Pyrrolo[2,1-F][1,2,4]triazine derivatives as DYRK1A inhibitors

Abstract

Disclosed is a pyrrolo[2,1-f][1,2,4]triazine compound for treating various diseases and conditions.More specifically, the disclosure relates to the use of pyrrolo[2,1-f][1,2,4]triazine compound or its analogs in treating disorders characterized by overexpression of DYRKIA, such as cancer, Down's syndrome, Alzheimer's disease, diabetes, viral infections, and osteoarthritis. TIFF2024539620000669.tif30128

Description

[Technical field]

[0001] Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 254,733, filed October 12, 2021, and U.S. Provisional Application No. 63 / 347,757, filed June 1, 2022, which are incorporated by reference in their entireties.

[0002] Technical Field The present disclosure relates to a dual specificity tyrosine phosphorylation-regulated 1A kinase inhibitor and the composition comprising the same. More specifically, the present disclosure relates to the use of pyrrolo[2,1-f][1,2,4]triazine compound or its salt or analog in the treatment of disorders characterized by abnormal expression and / or activity of DYRK1A, such as cancer, Down's syndrome, Alzheimer's disease, diabetes, viral infection and osteoarthritis. [Background technology]

[0003] Background Dual specificity tyrosine phosphorylation regulated kinases (DYRK1A, 1B, 2-4) comprise a family of protein kinases within the CMGC group of the eukaryotic kinome. These protein kinases are involved in multiple cellular functions, including intracellular signal transduction, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine / methionine / folate regulation, thermoregulation, endocytosis, neuronal development, synaptic plasticity, and others. Aberrant expression and / or activity of some of these kinases, particularly DYRK1A, is seen in many human nervous system diseases, such as cognitive impairment associated with Down syndrome, Alzheimer's disease, and related disorders, tauopathies, dementia, Pick's disease, Parkinson's disease, and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorders. DYRKs are also involved in diabetes, abnormal folate / methionine metabolism, osteoarthritis, some solid cancers (glioblastoma, breast cancer, and pancreatic cancer) and leukemia (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), and infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium) (International Journal of Molecular Sciences (2021), 22(11), 6047 (Non-Patent Document 1)). DYRK1A has also been identified as a critical stabilizer of EGFR, a crucial factor leading to keratinization, cellular hyperproliferation, abnormal differentiation, and inflammatory infiltration during the progression of psoriasis (Cell Death & Disease (2019), 10, 282 (Non-Patent Document 2)). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] International Journal of Molecular Sciences (2021), 22(11), 6047 [Non-Patent Document 2] Cell Death & Disease (2019), 10, 282 Summary of the Invention

[0005] overview The disclosure provides methods and reagents that include contacting cells with an agent, such as a pyrrolo[2,1-f][1,2,4]triazine compound, in an amount sufficient to antagonize DYRK1A activity, for example, to reduce the proliferation of head and neck squamous cell carcinoma, luminal / HER2 breast cancer (Cell (2016), 164(1-2), 293-309), or pancreatic adenocarcinoma, as well as to reduce the self-renewal capacity of glioblastoma, and to reduce the viability of ovarian cancer spheroid cells (Molecular Cancer Research (2017), 15(4), 371-381).

[0006] The disclosure also provides methods and reagents that involve contacting a cell with an agent, such as a pyrrolo[2,1-f][1,2,4]triazine compound, in an amount sufficient to antagonize DYRK1A activity, e.g., i) to normalize prenatal and early postnatal brain development; ii) to improve cognitive function in adolescents and adults; and / or iii) to attenuate Alzheimer's type neurodegeneration.

[0007] Some embodiments disclosed herein include DYRK1A inhibitors that contain a pyrrolo[2,1-f][1,2,4]triazine core. Other embodiments disclosed herein include pharmaceutical compositions and methods of treatment using these compounds.

[0008] One embodiment disclosed herein is a compound having the structure of Formula I: TIFF2024539620000002.tif31128 or a pharma- ceutically acceptable salt thereof, During the ceremony, R 1 is 1 to 10 R 3 is heteroaryl optionally substituted with R 2 is unsubstituted -(C1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~3 Alkylene) p OR 4 , 1 to 10 R 5 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, 1 to 10 R 6 -heteroaryl, optionally substituted with, and 1 to 12 R 7 may be substituted with -(C 1~5 Alkylene) p carbocyclyl, wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 alkyl); Each R 3 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 8 , 1 to 10 R 9 -heterocyclyl, optionally substituted with 1 to 12 R 10 -carbocyclyl, -C(=O)N(R 11 )2, and -C(=O)R 12 wherein -(C 1~5 Alkylene) is 1-5 halogenated and / or 1-3 unsubstituted -(C 1~3 alkyl); Each R 4 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9haloalkyl); Each R 5 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -OMe; Each R 6 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -OMe; Each R 7 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -N(R 13 )2, -(C 1~5 Alkylene) p OR 14 , and 1 to 10 R 15 -heterocyclyl, optionally substituted with -(C 1~5 Alkylene) is 1-5 halogenated and / or 1-3 unsubstituted -(C 1~3 alkyl); Each R 8 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 9 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9haloalkyl); Each R 10 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 11 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), 1 to 12 R 16 may be substituted with -(C 1~5 Alkylene) p Carbocyclyl, 1 to 10 R 17 -heterocyclyl, optionally substituted with 1 to 10 R 18 -heteroaryl, optionally substituted with -(C 1~5 Alkylene) is 1-5 halogenated and / or 1-3 unsubstituted -(C 1~3 alkyl); Each R 12 is 1 to 10 R 17 -heterocyclyl optionally substituted with; Each R 13 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 14 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 15 are independently halide, unsubstituted -(C1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 16 are independently halide, -OMe, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 17 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 18 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); each p is independently 0 or 1; Here each H atom is independently 2 It may be replaced by H(D) (deuterium).

[0009] Another embodiment disclosed herein is a compound having the structure of Formula I: TIFF2024539620000003.tif31128 or a pharma- ceutically acceptable salt thereof, During the ceremony, R 1 is 1 to 10 R 3 is heteroaryl optionally substituted with R 2 is unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 4 , 1 to 10 R 5 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, 1 to 10 R 6 -heteroaryl, optionally substituted with, and 1 to 12 R 7 may be substituted with -(C 1~5 Alkylene) p carbocyclyl, wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 alkyl); Each R 3 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 8 , -(C 1~5 alkylene)CN, 1 to 10 R 9 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, 1 to 12 R 10 -carbocyclyl, optionally substituted with 1 to 10 R 19 may be substituted with -(C 1~5 Alkylene) p Heteroaryl, -(C 1~5 Alkylene) p C(=O)N(R 11 )2, and -C(=O)R 12 wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 alkyl); Each R 4are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 5 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), 1 to 10 R 15 -heterocyclyl, -(C 1~5 Alkylene) p OR 20 , -SO2R 22 , and -C(=O)R 23 wherein -(C 1~5 Alkylene) is 1-5 halogenated and / or 1-3 unsubstituted -(C 1~3 alkyl); Alternatively, two R attached to the same carbon atom 5 together form a carbonyl group; Each R 6 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -OMe; Each R 7 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -N(R 13 )2, -(C 1~5 Alkylene) p OR 14 , 1 to 10 R 15 may be substituted with -(C 1~5 Alkylene)p Heterocyclyl, -C(=O)R 21 , and -NHC(=O)R 22 wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 alkyl); Each R 8 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 9 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 10 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 11 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), 1 to 12 R 16 may be substituted with -(C 1~5 Alkylene) p Carbocyclyl, 1 to 10 R 17 -heterocyclyl, optionally substituted with 1 to 10 R 18 -heteroaryl, optionally substituted with -(C 1~5 Alkylene) is 1-5 halogenated and / or 1-3 unsubstituted -(C1~3 alkyl); Each R 12 is 1 to 10 R 17 -heterocyclyl optionally substituted with; Each R 13 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 14 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -(C 1~5 Alkylene) p OR 20 selected from the group consisting of; Each R 15 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 16 are independently halide, -OMe, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 17 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 18 are independently halide, unsubstituted -(C 1~9alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 19 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 20 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 21 are independently 1 to 10 R 17 -heterocyclyl, -N(R 11 )2, and -OR 20 selected from the group consisting of; Each R 22 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 23 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and 1 to 12 R 24 -carbocyclyl, optionally substituted with; Each R 24 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9alkynyl), and unsubstituted -(C 1~9 haloalkyl); each p is independently 0 or 1; Here each H atom is independently 2 It may be replaced by H(D) (deuterium).

[0010] Another embodiment disclosed herein includes a compound having the structure of Formula I: R 1 is 1 to 10 R 3 is heteroaryl optionally substituted with R 2 is unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 4 , 1 to 10 R 5 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, 1 to 10 R 6 -heteroaryl, optionally substituted with, and 1 to 12 R 7 may be substituted with -(C 1~5 Alkylene) p carbocyclyl, wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 alkyl); Each R 3 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 8 , -(C 1~5 alkylene)CN, 1 to 10 R 9may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, 1 to 12 R 10 -carbocyclyl, optionally substituted with 1 to 10 R 19 may be substituted with -(C 1~5 Alkylene) p Heteroaryl, -(C 1~5 Alkylene) p C(=O)N(R 11 )2, and -C(=O)R 12 wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 alkyl); Each R 4 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 5 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), 1 to 10 R 15 -heterocyclyl, -(C 1~5 Alkylene) p OR 20 , -SO2R 22 , and -C(=O)R 23 wherein -(C 1~5 Alkylene) is 1-5 halogenated and / or 1-3 unsubstituted -(C 1~3 alkyl); Alternatively, two R attached to the same carbon atom 5 together form a carbonyl group; Each R 6 are independently halide, unsubstituted -(C 1~9alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -OMe; Each R 7 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -N(R 13 )2, -(C 1~5 Alkylene) p OR 14 , 1 to 10 R 15 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, -C(=O)R 21 , and -NH(=O)R 22 wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 alkyl); Each R 8 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 9 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 10 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9haloalkyl); Each R 11 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), 1 to 12 R 16 may be substituted with -(C 1~5 Alkylene) p Carbocyclyl, 1 to 10 R 17 -heterocyclyl, optionally substituted with 1 to 10 R 18 -heteroaryl, optionally substituted with -(C 1~5 Alkylene) is 1-5 halogenated and / or 1-3 unsubstituted -(C 1~3 alkyl); Each R 12 is 1 to 10 R 17 -heterocyclyl optionally substituted with; Each R 13 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 14 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -(C 1~5 Alkylene) p OR 20 selected from the group consisting of; Each R 15 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Alternatively, two R attached to the same carbon atom 15 together form a carbonyl group; Each R 16 are independently halide, -OMe, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 17 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 18 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 19 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 20 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); Each R 21 are independently 1 to 10 R 17 -heterocyclyl, -N(R 11 )2, and -OR 20 selected from the group consisting of; Each R22 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -(C 1~5 Alkylene) p OR 20 selected from the group consisting of; Each R 23 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and 1 to 12 R 24 -carbocyclyl, optionally substituted with; Each R 24 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl); each p is independently 0 or 1; Here each H atom is independently 2 It may be replaced by H(D) (deuterium).

[0011] Some embodiments include stereoisomers and pharma- ceutically acceptable salts of the compounds of formula (I).Some embodiments include pharma- ceutically acceptable salts of the compounds of formula (I).

[0012] Some embodiments include prodrugs of compounds of formula (I).

[0013] Some aspects of the disclosure include pharmaceutical compositions comprising a compound of formula (I) and a pharma- ceutically acceptable carrier, diluent, or excipient.

[0014] Other embodiments disclosed herein include methods of inhibiting DYRK1A by administration to patients suffering from diseases or disorders in which overexpression of DYRK1A is implicated, such as Alzheimer's disease, amyotrophic lateral sclerosis, CDKL5 deficiency disorder, Down's syndrome, frontotemporal dementia with parkinsonism-17 (FTDP-17), dementia with Lewy bodies, Parkinson's disease, Pick's disease, and additional diseases involving significant neurodegeneration, such as autism, dementia, epilepsy, Huntington's disease, multiple sclerosis; diseases and disorders associated with acquired brain injury, such as chronic traumatic encephalopathy, traumatic brain injury, tumors, and stroke.

[0015] DYRK1A inhibitors can also be used to treat tauopathy. Tauopathy is a neurodegenerative disorder characterized by the accumulation of abnormal tau protein in the brain. The scope of tau pathology extends beyond traditionally considered disease forms such as Pick's disease, progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. Emerging disease entities and conditions include globular glial tauopathy, primary age-related tauopathy including neurofibrillary tangle dementia, chronic traumatic encephalopathy (CTE), frontotemporal lobar degeneration with tau inclusions (FTLD-tau), and age-related tau astrogliopathy. Clinical manifestations include frontotemporal dementia, corticobasal syndrome, Richardson's syndrome, parkinsonism, pure akinesia with freezing of gait, and rarely motor neuron symptoms or cerebellar ataxia (Handbook of Clinical Neurology (2018), 145, 355-368 and Aging Cell (2019), 18(5), e13000).

[0016] DYRK1A inhibitors may also be used to treat disorders associated with abnormal folate / methionine metabolism.

[0017] Non-limiting examples of diseases treatable with the compounds and compositions provided herein include various cancers, diabetes, psoriasis, knee osteoarthritis, tendon disorders, human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), hepatitis C virus (HCV), and herpes simplex virus type 1 (HSV-1).

[0018] Some aspects of the disclosure include methods for preparing compounds of formula (I).

[0019] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present disclosure, as claimed. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Detailed Description Compositions and methods for inhibiting DYRK1A are provided herein.

[0021] Some embodiments provided herein relate to methods for treating diseases including, but not limited to, neurological diseases or disorders, cancer, cognitive disorders, knee osteoarthritis, tendon disorders, viral infections, single-cell parasitic infections, and movement disorders.

[0022] In some embodiments, non-limiting examples of neurological diseases or disorders treatable with the compounds and compositions provided herein include, but are not limited to, Alzheimer's disease, amyotrophic lateral sclerosis, Down's syndrome, frontotemporal dementia with parkinsonism-17 (FTDP-17), dementia with Lewy bodies, Parkinson's disease, Pick's disease, tauopathies, and additional diseases with significant neurodegeneration, such as autism, dementia, epilepsy, Huntington's disease, multiple sclerosis; diseases and disorders associated with acquired brain injury, such as chronic traumatic encephalopathy, traumatic brain injury, tumors, and stroke.

[0023] In some embodiments, non-limiting examples of cancers treatable with the compounds and compositions provided herein include solid cancers (e.g., glioblastoma, ovarian cancer, breast cancer, and pancreatic cancer), and leukemias (e.g., acute lymphoblastic leukemia, acute megakaryoblastic leukemia, and chronic myeloid leukemia).

[0024] In some embodiments, a pharmaceutical composition is provided that is effective for treating a disease in an animal, such as a mammal, caused by overexpression of DYRK1A, comprising a pharma- ceutically acceptable carrier and a compound described herein.

[0025] Definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this disclosure belongs.All patents, applications, published applications, and other publications are incorporated by reference in their entirety.In the event that there are multiple definitions for terms in this specification, the definitions in this section shall prevail unless otherwise stated.

[0026] As used herein, "alkyl" refers to a branched or straight chain chemical group containing only carbon and hydrogen, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, and neopentyl. Alkyl groups can be unsubstituted or substituted with one or more substituents. In some embodiments, alkyl groups contain 1-9 carbon atoms (e.g., 1-6 carbon atoms, 1-4 carbon atoms, or 1-2 carbon atoms).

[0027] As used herein, "alkenyl" refers to a straight or branched chain chemical group that contains only carbon and hydrogen and contains at least one carbon-carbon double bond, such as ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, and the like. In various embodiments, an alkenyl group can be unsubstituted or substituted with one or more substituents. Typically, an alkenyl group contains 2 to 9 carbon atoms (e.g., 2 to 6 carbon atoms, 2 to 4 carbon atoms, or 2 carbon atoms).

[0028] As used herein, "alkynyl" refers to a straight or branched chain chemical group that contains only carbon and hydrogen and contains at least one carbon-carbon triple bond, such as ethynyl, 1-propynyl, 1-butynyl, 2-butynyl, etc. In various embodiments, an alkynyl group can be unsubstituted or substituted with one or more substituents. Typically, an alkynyl group contains 2 to 9 carbon atoms (e.g., 2 to 6 carbon atoms, 2 to 4 carbon atoms, or 2 carbon atoms).

[0029] As used herein, "alkylene" refers to a branched or straight-chain divalent chemical group containing only carbon and hydrogen, such as methylene, ethylene, n-propylene, isopropylene, n-butylene, isobutylene, sec-butylene, tert-butylene, n-pentylene, isopentylene, sec-pentylene, and neopentylene. An alkylene group can be unsubstituted or substituted with one or more substituents. In some embodiments, an alkylene group contains 1 to 9 carbon atoms (e.g., 1 to 6 carbon atoms, 1 to 4 carbon atoms, or 1 to 2 carbon atoms).

[0030] As used herein, "alkenylene" refers to a branched or straight-chain divalent chemical group that contains only carbon and hydrogen and contains at least one carbon-carbon double bond, such as ethenylene, 1-propenylene, 2-propenylene, 2-methyl-1-propenylene, 1-butenylene, 2-butenylene, and the like. In various embodiments, an alkenylene group can be unsubstituted or substituted with one or more substituents. Typically, an alkenylene group contains 2 to 9 carbon atoms (e.g., 2 to 6 carbon atoms, 2 to 4 carbon atoms, or 2 carbon atoms).

[0031] As used herein, "alkynylene" refers to a branched or straight-chain divalent chemical group that contains only carbon and hydrogen and contains at least one carbon-carbon triple bond, such as ethynylene, 1-propynylene, 1-butynylene, 2-butynylene, and the like. In various embodiments, an alkynylene group can be unsubstituted or substituted with one or more substituents. Typically, an alkynylene group contains 2 to 9 carbon atoms (e.g., 2 to 6 carbon atoms, 2 to 4 carbon atoms, or 2 carbon atoms).

[0032] As used herein, "alkoxy" refers to an alkyl-O- group, wherein the alkyl group is as described herein. Exemplary alkoxy groups include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, pentoxy, hexoxy, and heptoxy, as well as linear or branched positional isomers thereof.

[0033] As used herein, "haloalkoxy" refers to a haloalkyl-O- group, in which the haloalkyl group is as described herein. Exemplary haloalkoxy groups include fluoromethoxy, difluoromethoxy, trifluoromethoxy, and linear or branched positional isomers thereof.

[0034] As used herein, "carbocyclyl" refers to a ring system containing only carbon atoms in the ring system backbone, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cyclohexenyl. A carbocyclyl may contain multiple fused rings. A carbocyclyl may have any degree of saturation, provided that no ring in the ring system is aromatic. A carbocyclyl group may be unsubstituted or substituted with one or more substituents. In some embodiments, a carbocyclyl group contains 3 to 10 carbon atoms, such as 3 to 6 carbon atoms.

[0035] As used herein, "aryl" refers to a monocyclic, bicyclic, tricyclic, or polycyclic group in which only carbon atoms are present in the ring backbone, and which has 5 to 14 ring atoms, or alternatively 5, 6, 9, or 10 ring atoms; 6, 10, or 14 pi-electrons shared in the cyclic arrangement; and at least one ring in the system is aromatic. Aryl groups can be unsubstituted or substituted with one or more substituents. Examples of aryl include phenyl, naphthyl, tetrahydronaphthyl, 2,3-dihydro-1H-indenyl, and the like. In some embodiments, the aryl is phenyl.

[0036] As used herein, "arylalkylene" refers to an aryl-alkylene-group in which the aryl and alkylene portions are as previously described. In some embodiments, the arylalkylene group is 1~4 Contains an alkylene moiety. Exemplary arylalkylene groups include benzyl and 2-phenethyl.

[0037] The term "heteroaryl" as used herein means a monocyclic, bicyclic, tricyclic, or polycyclic group having 5 to 14 ring atoms, or alternatively 5, 6, 9, or 10 ring atoms; having 6, 10, or 14 pi electrons shared in a cyclic arrangement; and at least one ring in the system is aromatic and contains one or more heteroatoms independently selected from the group consisting of N, O, and S. Heteroaryl groups can be unsubstituted or substituted with one or more substituents. Examples of heteroaryl include thienyl, pyridinyl, furyl, oxazolyl, oxadiazolyl, pyrrolyl, imidazolyl, triazolyl, thiodiazolyl, pyrazolyl, isoxazolyl, thiadiazolyl, pyranyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, benzothienyl, benzoxadiazolyl, benzofuranyl, benzimidazolyl, benzotriazolyl, cinnolinyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, naphthyridinyl, purinyl, thienopyridinyl, pyrido[2,3 -d]pyrimidinyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl, quinolinyl, thieno[2,3-c]pyridinyl, pyrazolo[3,4-b]pyridinyl, pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridine, pyrazolo[4,3-b]pyridinyl, tetrazolyl, chroman, 2,3-dihydrobenzo[b][1,4]dioxine, benzo[d][1,3]dioxole, 2,3-dihydrobenzofuran, tetrahydroquinoline, 2,3-dihydrobenzo[b][1,4]oxathiin, isoindoline, etc. In some embodiments, heteroaryl is selected from thienyl, pyridinyl, furyl, pyrazolyl, imidazolyl, isoindolinyl, pyranyl, pyrazinyl, and pyrimidinyl.

[0038] As used herein, "halo", "halide", or "halogen" refers to a chloro, bromo, fluoro, or iodo atom radical. In some embodiments, the halo is chloro, bromo, or fluoro. For example, the halide can be fluoro.

[0039] As used herein, "haloalkyl" refers to a hydrocarbon substituent that is a linear or branched alkyl, alkenyl, or alkynyl substituted with one or more chloro, bromo, fluoro, and / or iodo atoms. In some embodiments, the haloalkyl is a fluoroalkyl in which one or more hydrogen atoms are replaced with fluoro. In some embodiments, the haloalkyl is 1-3 carbons long (e.g., 1-2 carbons long or 1 carbon long). The term "haloalkylene" refers to diradical variants of haloalkyl, which can act as spacers between groups, between atoms, or between a ring and another functional group.

[0040] As used herein, "heterocyclyl" refers to a non-aromatic ring system containing at least one heteroatom in the ring system backbone. Heterocyclyls, such as bicyclic and spirocyclic heterocyclyls, can contain multiple fused rings. Heterocyclyls can be substituted or unsubstituted with one or more substituents. In some embodiments, the heterocycle has 3-11 members. In 6-membered monocyclic heterocycles, the heteroatoms are selected from 1-3 O, N, and S, and when the heterocycle is 5-membered, it can have 1 or 2 heteroatoms selected from O, N, and S. Examples of heterocyclyl include azirinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, 1,4,2-dithiazolyl, dihydropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl, morpholinyl, thiomorpholinyl, piperazinyl, pyranyl, pyrrolidinyl, tetrahydrofuryl, tetrahydropyridinyl, oxazinyl, thiazinyl, thiinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl, piperidinyl, pyrazolidinyl, imidazolidinyl, thiomorpholinyl, etc. In some embodiments, heterocyclyl is selected from azetidinyl, morpholinyl, piperazinyl, pyrrolidinyl, and tetrahydropyridinyl.

[0041] As used herein, "monocyclic heterocyclyl" refers to a single non-aromatic ring containing at least one heteroatom in the ring system backbone. The heterocyclyl may be unsubstituted or substituted with one or more substituents. In some embodiments, the heterocycle has 3-7 members. In a 6-membered monocyclic heterocycle, the heteroatoms are selected from 1-3 O, N, and S, and when the heterocycle is 5-membered, it may have 1 or 2 heteroatoms selected from O, N, and S. Examples of monocyclic heterocyclyls include azirinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, 1,4,2-dithiazolyl, dihydropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl, morpholinyl, thiomorpholinyl, piperazinyl, pyranyl, pyrrolidinyl, tetrahydrofuryl, tetrahydropyridinyl, oxazinyl, thiazinyl, thiinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl, piperidinyl, pyrazolidinyl, imidazolidinyl, thiomorpholinyl, and the like.

[0042] As used herein, "bicyclic heterocyclyl" refers to a bicyclic non-aromatic ring system containing at least one heteroatom in the ring system backbone. The bicyclic heterocyclyl may be unsubstituted or substituted with one or more substituents. In some embodiments, the bicyclic heterocycle has 4-11 members and the heteroatoms are selected from 1-5 O, N, and S. Examples of bicyclic heterocyclyls include 2-azabicyclo[1.1.0]butane, 2-azabicyclo[2.1.0]pentane, 2-azabicyclo[1.1.1]pentane, 3-azabicyclo[3.1.0]hexane, 5-azabicyclo[2.1.1]hexane, 3-azabicyclo[3.2.0]heptane, octahydrocyclopenta[c]pyrrole, 3-azabicyclo[4.1.0]heptane, 7-azabicyclo[2.2.1]heptane, 6-azabicyclo[3.1.1]heptane, 7-azabicyclo[4.2.0]octane, 2-azabicyclo[2.2.2]octane, and the like.

[0043] As used herein, "spirocyclic heterocyclyl" refers to a bicyclic non-aromatic ring system containing at least one heteroatom in the ring system backbone, with the rings connected through only one atom. The spirocyclic heterocyclyl may be unsubstituted or substituted with one or more substituents. In some embodiments, the spirocyclic heterocycle has 5-11 members, with 1-5 heteroatoms selected from O, N, and S. Examples of spirocyclic heterocyclyls include 2-azaspiro[2.2]pentane, 4-azaspiro[2.5]octane, 1-azaspiro[3.5]nonane, 2-azaspiro[3.5]nonane, 7-azaspiro[3.5]nonane, 2-azaspiro[4.4]nonane, 6-azaspiro[2.6]nonane, 1,7-diazaspiro[4.5]decane, 2,5-diazaspiro[3.6]decane, and the like.

[0044] The term "substituted" refers to a moiety having a substituent replacing a hydrogen on one or more non-hydrogen atoms of a molecule. "Substituted" or "substituted with" is understood to include the implicit proviso that the substitution is made in accordance with the atom being replaced and the permissible valence of the substituent, and includes the implicit proviso that the substitution results in a stable compound, e.g., one that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, and the like. Substituents include, for example, one or more hydroxyl, -NH, -NH(C 1~3 alkyl), and -N(C 1~3 Optionally substituted with -(C alkyl) 1~9 Alkyl); -(C 1~9 haloalkyl; halide; hydroxyl; carbonyl [such as -C(O)OR and -C(O)R]; thiocarbonyl [such as -C(S)OR, -C(O)SR, and -C(S)R]; one or more halides, hydroxyl, -NH2, -NH(C 1~3 alkyl), and -N(C 1~3 Optionally substituted with -(C alkyl) 1~9alkoxy; -OPO(OH); phosphonates [such as -PO(OH) and -PO(OR')]; -OPO(OR')R''; -NRR'; -C(O)NRR'; -C(NR)NR'R''; -C(NR')R''; cyano; nitro; azido; -SH; -SR; -OSO(OR); sulfonates [such as -SO(OH) and -SO(OR)]; -SONR'R''; and -SOR, where R, R', and R'' each occurrence independently represent H; -(C 1~9 alkyl); C optionally substituted with 1 to 3 R''' 6~10 aryl; 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from N, O, and S and optionally substituted with 1-3 R'"; C optionally substituted with 1-3 R'"; 3~7 carbocyclyl; and 3-8 membered heterocyclyl having 1-4 heteroatoms independently selected from N, O, and S and optionally substituted with 1-3 R''', where each R''' is independently -(C 1~6 alkyl), -(C 1~6 haloalkyl), halide (e.g. F), hydroxyl, -C(O)OR, -C(O)R, -(C 1~6 R and R' are each independently selected from H and -(C(O)NRR', -alkoxyl), -NRR', -C(O)NRR', and cyano, 1~6 In some embodiments, the substituent is selected from -(C alkyl). 1~6 alkyl), -(C 1~6 haloalkyl), halide (e.g. F), hydroxyl, -C(O)OR, -C(O)R, -(C 1~6 R and R' are each independently selected from H and -(C(O)NRR', -alkoxyl), -NRR', -C(O)NRR', and cyano, 1~6 alkyl).

[0045] As used herein, when two groups are shown to be "linked" or "bonded" to form a "ring", it should be understood that a bond is formed between the two groups, and that the bond can include replacing a hydrogen atom on one or both groups with the bond to form a carbocyclyl ring, a heterocyclyl ring, an aryl ring, or a heteroaryl ring. Those skilled in the art will recognize that these rings can and are readily formed by routine chemical reactions. In some embodiments, these rings have 3 to 7 members, for example 5 or 6 members.

[0046] Those skilled in the art will recognize that some chemical structures described herein may be represented on paper in one or more other resonance forms, or may exist dynamically in one or other tautomeric forms, and that these tautomeric forms represent only a small sample of these compounds. Although these resonance forms or tautomers are not expressly represented herein, these compounds are expressly contemplated as being within the scope of the present disclosure.

[0047] The compounds provided herein may include various stereochemical forms.The compounds also include diastereomers and optical isomers resulting from structural asymmetry in certain compounds, such as enantiomeric mixtures, including racemic mixtures, and individual enantiomers and diastereomers.Separation of individual isomers or selective synthesis of individual isomers can be achieved by applying various methods well known to those skilled in the art.Unless otherwise indicated, when the disclosed compound is named or illustrated by a structure without specifying the stereochemical structure and has one or more chiral centers, it is understood that the disclosed compound represents all possible stereoisomers of the compound.

[0048] The present disclosure includes all pharma- ceutically acceptable isotopically labeled compounds of formula I in which one or more atoms are replaced by an atom having the same atomic number but an atomic mass or atomic mass number different from the atomic mass or atomic mass number predominant in nature. Examples of isotopes suitable for inclusion in the compounds of the present disclosure include: 2 H (deuterium) and 3 Hydrogen isotopes such as H (tritium), 11 C. 13 C, and 14 Carbon isotopes such as C, 36 Chlorine isotopes such as Cl, 18 Fluorine isotopes such as F, 123 I and 125 Iodine isotopes such as I 13 N and 15 Nitrogen isotopes such as N 15 O. 17 O, and 18 Oxygen isotopes such as O 32 Phosphorus isotopes such as P, as well as 35 S isotopes such as, but not limited to, S.

[0049] The term "administration" or "administering" refers to a method of providing a dosage form of a compound or pharmaceutical composition to a vertebrate or invertebrate, including a mammal, bird, fish, or amphibian, such as oral, subcutaneous, intravenous, intralymphatic, intranasal, topical, transdermal, intraperitoneally, intramuscular, intrapulmonary, vaginal, rectal, otological, neuro-otological, intraocular, subconjunctival, anterior chamber injection, intravitreal, intraperitoneal, intrathecal, intrathecal, intraperitoneal ... By this is meant a method of administration by application intracavitary, intracystic, intrapleural, wound irrigation, intrabuccal, intraperitoneal, intra-articular, intraauricular, intrabronchial, intravesical, intrameningeal, inhalation, intratracheal or intrabronchial instillation, direct injection into pulmonary cavities, intraspinal, intra-articular bursa, intrathoracic, thoracic fistula irrigation, epidural, intratympanic, intracisternal, intravascular, intraventricular, intraosseous, irrigation of infected bone, or as part of any admixture with a prosthesis. The method of administration may vary depending on a variety of factors, such as the components of the pharmaceutical composition, the site of the disease, the disease involved, and the severity of the disease.

[0050] As used herein, a "diagnostic" refers to a compound, method, system, or device that aids in the identification or characterization of a health or disease state. Diagnostics can be used in standard assays known in the art.

[0051] The term "mammal" is used in its ordinary biological sense, and thus specifically includes humans, cows, horses, monkeys, dogs, cats, mice, rats, cows, sheep, pigs, goats, and non-human primates, but also many other species.

[0052] The terms "pharmaceutically acceptable carrier", "pharmaceutically acceptable diluent" and "pharmaceutically acceptable excipient" include any solvent, cosolvent, complexing agent, dispersion medium, coating, isotonicity agent, absorption retardant, and the like that is not biologically or otherwise undesirable. The use of these media and agents for pharmaceutically active substances is well known in the art. Any conventional media or agent is contemplated for use in therapeutic compositions unless it is incompatible with the active ingredient. Supplementary active ingredients can also be incorporated into the composition. In addition, various auxiliary agents, such as those commonly used in the art, can be included. These and other similar compounds are described in the literature, for example, in the Merck Index, Merck & Company, Rahway, NJ. Reviews of the inclusion of various ingredients in pharmaceutical compositions are provided, for example, in Gilman et al. (Eds.) (2010); Goodman and Gilman's: The Pharmacological Basis of Therapeutics , 12th Ed., The McGraw-Hill Companies It is described in.

[0053] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological effectiveness and properties of the compounds provided herein and is not biologically or otherwise undesirable. In many cases, the compounds provided herein can form acid and / or base salts due to the presence of amino and / or carboxyl groups or groups similar thereto. Many of these salts are known in the art, for example, as described in WO 87 / 05297. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like, with ammonium, potassium, sodium, calcium, and magnesium salts being particularly preferred. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.

[0054] As used herein, a "patient" refers to a human or non-human animal, such as a dog, cat, mouse, rat, cow, sheep, pig, goat, non-human primate or bird, such as a chicken, and any other vertebrate or invertebrate. In some embodiments, the patient is a human.

[0055] A "therapeutically effective amount" of a compound provided herein is an amount sufficient to obtain a desired physiological effect, and may vary according to the nature and severity of the disease state and the efficacy of the compound. A "therapeutically effective amount" is also intended to include a combination of one or more compounds of formula I with one or more other agents effective for treating the diseases and / or conditions described herein. The combination of compounds may be a synergistic combination. Synergism, for example as described in Chou and Talalay, Advances in Enzyme Regulation (1984), 22, 27-55, occurs when the effect of the compounds administered in combination exceeds the additive effect of the compounds administered alone as a single agent. In general, synergistic effects are most evident at suboptimal concentrations of the compounds. It will be recognized that different concentrations may be used for the prevention and treatment of active disease. Furthermore, this amount may depend on the height, weight, sex, age, and medical history of the patient.

[0056] A therapeutic effect is one which relieves to some extent one or more symptoms of the disease.

[0057] As used herein, "treat", "treatment" or "treating" refers to administering a compound or pharmaceutical composition provided herein for therapeutic purposes. The term "therapeutic treatment" refers to administering treatment to a patient already suffering from a disease to cause a therapeutically beneficial effect, such as ameliorating existing symptoms, ameliorating the metabolic causes underlying the symptoms, postponing or preventing further development of the disorder, and / or reducing the severity of symptoms that have developed or are expected to develop.

[0058] As used herein, "drug elution" and / or controlled release refers to any mechanism by which a drug contained in a drug eluting material passes through the material over time into surrounding body tissues, e.g., diffusion, migration, permeation, and / or desorption.

[0059] As used herein, "drug eluting material" and / or controlled release material means any natural, synthetic, or semi-synthetic material that is capable of acquiring and retaining a desired shape or configuration, that has one or more drugs incorporated therein, and that the incorporated drugs can be eluted therefrom over time.

[0060] As used herein, "elutable drug" means any drug or combination of drugs that has the ability to pass over time through the drug eluting material in which it is contained and into the surrounding area of ​​the body.

[0061] Compound The compounds and compositions described herein can be used to inhibit DYRK1A for the treatment of diseases or disorders in which overexpression of DYRK1A is implicated, such as neurological diseases or disorders, cancer, cognitive disorders, knee osteoarthritis, tendon disorders, viral infections, single-cell parasitic infections, and movement disorders.

[0062] Some embodiments of the present disclosure include a compound of formula I: TIFF2024539620000004.tif31128 or a salt thereof, a pharma- ceutically acceptable salt, or a prodrug thereof.

[0063] In some embodiments of Formula I, R 1 is 1 to 10 R 3 In some embodiments, R 1 is 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1 R 3 and optionally substituted heteroaryl.

[0064] In some embodiments of Formula I, R 1 is 1 to 10 (e.g. 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 3 may be substituted with TIFF2024539620000005.tif121153.

[0065] In some embodiments of Formula I, R 1 is 1 to 10 (e.g. 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 3 may be substituted with TIFF2024539620000006.tif21128.

[0066] In some embodiments of Formula I, R 1 is 1 to 3 (e.g. 1 to 2, 1) R 3 may be substituted with TIFF2024539620000007.tif21128.

[0067] In some embodiments of Formula I, R 1 1 to 3 R 3 may be substituted with TIFF2024539620000008.tif26136.

[0068] R 1 But non-substitution The compound according to any one of claims 1 to 3, selected from the group consisting of TIFF2024539620000009.tif26136.

[0069] In some embodiments of Formula I, R 2 is unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~3 Alkylene) p OR 4 , 1-10 (e.g. 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 1) R5 may be substituted with -(C 1~5 Alkylene) p heterocyclyl, 1-10 (e.g. 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 1) R 6 -heteroaryl, optionally substituted with, and 1 to 12 (e.g., 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 7 may be substituted with -(C 1~5 Alkylene) p carbocyclyl, wherein each -(C 1~5 alkylene) independently represents 1 to 5 (e.g., 1 to 4, 1 to 3, 1 to 2, 1) halides (e.g., F, Cl, Br, I) and / or 1 to 3 (e.g., 1 to 2, 1) unsubstituted -(C 1~3 It may be substituted with alkyl.

[0070] In some embodiments of Formula I, R 2 is unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 4 , 1 to 10 R 5 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, 1 to 10 R 6 -heteroaryl, optionally substituted with, and 1 to 12 R 7 may be substituted with -(C 1~5 Alkylene) p carbocyclyl, wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 It may be substituted with alkyl.

[0071] In some embodiments of Formula I, R 2 is unsubstituted -(C 1~9 alkyl), unsubstituted -(C 1~9 haloalkyl), 1 to 10 (e.g. 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 5 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, 1 to 10 R 6 -heteroaryl, optionally substituted with, and 1 to 12 (e.g., 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 7 may be substituted with -(C 1~5 Alkylene) p carbocyclyl, wherein each -(C 1~5 alkylene) independently represents 1 to 5 (e.g., 1 to 4, 1 to 3, 1 to 2, 1) halides (e.g., F, Cl, Br, I) and / or 1 to 3 (e.g., 1 to 2, 1) unsubstituted -(C 1~3 It may be substituted with alkyl.

[0072] In some embodiments of Formula I, R 2 is unsubstituted -(C 1~5 alkyl), unsubstituted -(C 1~5 haloalkyl), 1 to 3 (e.g. 1 to 2, 1) R 5 may be substituted with -(C 1~2 Alkylene) p heterocyclyl and 1-3 (e.g. 1-2, 1) R 7 may be substituted with -(C 1~2 Alkylene) p carbocyclyl, wherein each -(C 1~5 Alkylene) may be independently substituted with 1 to 2 halides.

[0073] In some embodiments of Formula I, R 2 is unsubstituted -(C 1~5 alkyl), unsubstituted -(C 2~5alkenyl), unsubstituted -(C 2~5 alkynyl), unsubstituted -(C 1~5 haloalkyl), -(C 1~2 Alkylene) p OR 4 , 1 to 3 R 5 may be substituted with -(C 1~2 Alkylene) p Heterocyclyl, 1 to 3 R 6 -heteroaryl, optionally substituted with, and 1 to 3 R 7 may be substituted with -(C 1~2 Alkylene) p carbocyclyl, wherein each -(C 1~2 Alkylene) may be independently substituted with 1 to 2 halides.

[0074] In some embodiments of Formula I, R 2 1 to 3 R 5 may be substituted with -(C 1~2 Alkylene) p heterocyclyl, where -(C 1~5 alkylene) may be optionally substituted with one to two halides, and the heterocyclyl is selected from the group consisting of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, oxaspiro[3.3]heptanyl, and oxaspiro[3.3]heptanyl.

[0075] In some embodiments of Formula I, R 2 teeth TIFF2024539620000010.tif50153, wherein each R 7 is independently selected from the group consisting of F, Me, -CHF, -CHF2, -CF3, -CHOH, -CH2OMe, -OH, -OMe, -OEt, -OCD3, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCH2CH2OMe, -OCH2CH2OH, -NH2, -NHMe, and -NMe2.

[0076] In some embodiments of Formula I, R 2 teeth TIFF2024539620000011.tif31147, wherein each R 7 is independently selected from the group consisting of F, Me, -CHF2, -CH2OMe, -OH, -OMe, -OCD3, -OCH2CHF2, and -OCH2CH2OMe.

[0077] In some embodiments of Formula I, R 2 teeth TIFF2024539620000012.tif107152, wherein each R 7 are independently F, Me, Et, iPr, iBu, -CH2F, -CHF2, -CF3, -CH2OH, -CH2OMe, -OH, -OMe, -OEt, -OCD3, -OCF3, -CH 2CH2F, -CH2CHF2, -CH2CF3, -CH2CH2CF3, -CH2CH2OMe, -CH2CH2OH, -C(=O)Me, -C(=O)Et, -C(=O)iPr, TIFF2024539620000013.tif10128, and -SO2Me, with the proviso that F, -OH, -OMe, -OEt, -OCD3, and -OCF3 are not bonded to N.

[0078] In some embodiments of Formula I, R 2 teeth TIFF2024539620000014.tif72153, wherein each R 7 are independently selected from the group consisting of F, Me, iBu, -OH, -OMe, -CH2CH2F, -CH2CHF2, -CH2CF3, -CH2CH2CF3, -CH2CH2OMe, -CH2CH2OH, -C(=O)Me, -C(=O)Et, and -C(=O)iPr, with the proviso that F, -OH, -OMe are not bonded to N.

[0079] In some embodiments of Formula I, R 2 1 to 2 R 6and optionally substituted -heteroaryl, where heteroaryl is pyrazolyl.

[0080] In some embodiments of Formula I, R 2 1 to 3 R 7 may be substituted with -(C 1~2 Alkylene) p carbocyclyl, where -(C 1~5 The alkylene) may be optionally substituted with one to two halide radicals, and the carbocyclyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and spiro[3.3]heptanyl.

[0081] In some embodiments of Formula I, each R 3 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 8 , 1-10 (e.g. 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 1) R 9 -heterocyclyl, 1 to 12 (e.g., 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 10 -carbocyclyl, -C(=O)N(R 11 )2, and -C(=O)R 12 wherein -(C 1~5 Alkylene) is substituted with 1-5 (e.g. 1-4, 1-3, 1-2, 1) halides (e.g. F, Cl, Br, I) and / or 1-3 (e.g. 1-2, 1) unsubstituted -(C 1~3 It may be substituted with alkyl.

[0082] In some embodiments of Formula I, each R 3are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 8 , -(C 1~5 alkylene)CN, 1 to 10 R 9 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, 1 to 12 R 10 -carbocyclyl, optionally substituted with 1 to 10 R 19 may be substituted with -(C 1~5 Alkylene) p Heteroaryl, -(C 1~5 Alkylene) p C(=O)N(R 11 )2, and -C(=O)R 12 wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 It may be substituted with alkyl.

[0083] In some embodiments of Formula I, each R 3 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 1~9 haloalkyl), -(C 1~5 Alkylene) p OR 8 , 1-10 (e.g. 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 1) R 9 -heterocyclyl, 1 to 12 (e.g., 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 10 -carbocyclyl, optionally substituted with -C(=O)R 12 wherein -(C 1~5Alkylene) is substituted with 1-5 (e.g. 1-4, 1-3, 1-2, 1) halides (e.g. F, Cl, Br, I) and / or 1-3 (e.g. 1-2, 1) unsubstituted -(C 1~3 It may be substituted with alkyl.

[0084] In some embodiments of Formula I, each R 3 are independently halide, unsubstituted -(C 1~5 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~5 alkynyl), unsubstituted -(C 1~5 haloalkyl), -(C 1~4 Alkylene) p OR 8 , -(C 1~2 Alkylene) p OR 8 , -(C 1~4 alkylene)CN, -(C 1~2 alkylene)CN, optionally substituted with 1 to 2 R9 -(C 1~2 Alkylene) p Heterocyclyl, 1-2 R 10 -carbocyclyl, optionally substituted with 1 to 2 R 19 may be substituted with -(C 1~2 Alkylene) p Heteroaryl, -(C 1~2 Alkylene) p C(=O)N(R 11 )2, and -C(=O)R 12 wherein each -(C 1~2 alkylene) or -(C 1~4 Alkylene) may be independently substituted with 1 to 2 halides.

[0085] In some embodiments of Formula I, each R 3 are independently F, Cl, unsubstituted -(C 1~5 alkyl), unsubstituted -(C 1~5 haloalkyl), -(C 1~4 Alkylene) p OH, -(C 1~2 Alkylene) pOMe, -(C 1~4 alkylene)CN, -(C 1~2 alkylene)CN, 1 to 2 R 9 may be substituted with -(CH2) p Heterocyclyl, 1-2 R 10 -carbocyclyl, optionally substituted with 1 to 2 R 19 may be substituted with -(CH2) p Heteroaryl, -(CH2)C(=O)N(Me)2, and -C(=O)R 12 wherein each -(C 1~2 alkylene) or -(C 1~4 Alkylene) may be independently substituted with 1 to 2 halides.

[0086] In some embodiments of Formula I, each R 3 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~4 alkyl), unsubstituted -(C 1~4 haloalkyl), 1 to 3 (e.g. 1 to 2, 1) R 9 -heterocyclyl, optionally substituted with, and 1 to 3 (e.g., 1 to 2, 1) R 10 -carbocyclyl, optionally substituted with

[0087] In some embodiments of Formula I, each R 3 are independently halide, unsubstituted -(C 1~3 alkyl), unsubstituted -(C 1~3 haloalkyl), -(C 1~3 Alkylene) p OR 8 , heterocyclyl optionally substituted with 1 to 2 R 10 -carbocyclyl, optionally substituted with -C(=O)R 12 is selected from the group consisting of:

[0088] In some embodiments of Formula I, each R 3is independently selected from the group consisting of chloro, methyl, ethyl, isopropyl, 2-fluoroethyl, 2,2-difluoroethyl, methoxy, methoxymethyl, tetrahydropyranyl, difluorocyclobutyl, and (pyrrolidin-1-yl)methanone.

[0089] In some embodiments of Formula I, each R 4 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0090] In some embodiments of Formula I, each R 4 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0091] In some embodiments of Formula I, each R 4 are independently H, unsubstituted -(C 1~5 alkyl), unsubstituted -(C 2~5 alkenyl), unsubstituted -(C 2~5 alkynyl), and unsubstituted -(C 1~5 haloalkyl).

[0092] In some embodiments of Formula I, each R 4 are independently H, unsubstituted -(C 1~3 alkyl), and unsubstituted -(C 1~3 haloalkyl).

[0093] In some embodiments of Formula I, each R 5 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9alkynyl), unsubstituted -(C 1~9 haloalkyl), and -OMe.

[0094] In some embodiments of Formula I, each R 5 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), 1 to 10 (e.g. 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 15 -heterocyclyl, -(C 1~5 Alkylene) p OR 20 , -SO2R 22 , and -C(=O)R 23 wherein -(C 1~5 Alkylene) is 1-5 halogenated and / or 1-3 unsubstituted -(C 1~3 It may be substituted with alkyl.

[0095] In some embodiments of Formula I, each R 5 are independently F, Cl, unsubstituted -(C 1~5 alkyl), unsubstituted -(C 1~5 haloalkyl), 1 to 2 R 15 -heterocyclyl, -(C 1~2 Alkylene) p OR 20 , -SO2R 22 , and -C(=O)R 23 wherein -(C 1~2 Alkylene) may be substituted with 1 to 2 halides.

[0096] In some embodiments of Formula I, each R 5 are independently F, Cl, unsubstituted -(C 1~5 alkyl), unsubstituted -(C 1~5 haloalkyl), 1 to 2 R 15-heterocyclyl, -OH, -OMe, -SOMe, and -C(=O)R 23 is selected from the group consisting of:

[0097] In some embodiments of Formula I, two R 5 together form a carbonyl group.

[0098] In some embodiments of Formula I, each R 6 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -OMe.

[0099] In some embodiments of Formula I, each R 6 is independently selected from the group consisting of F, Cl, Me, CF3, and -OMe.

[0100] In some embodiments of Formula I, each R 7 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -N(R 13 )2, -(C 1~5 Alkylene) p OR 14 , and 1–10 (e.g., 1–9, 1–8, 1–7, 1–6, 1–5, 1–4, 1–3, 1–2, 1) R 15 -heterocyclyl, optionally substituted with -(C 1~5 Alkylene) is substituted with 1-5 (e.g. 1-4, 1-3, 1-2, 1) halides (e.g. F, Cl, Br, I) and / or 1-3 (e.g. 1-2, 1) unsubstituted -(C 1~3 It may be substituted with alkyl.

[0101] In some embodiments of Formula I, each R 7 are independently halide, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), -N(R 13 )2, -(C 1~5 Alkylene) p OR 14 , 1 to 10 R 15 may be substituted with -(C 1~5 Alkylene) p Heterocyclyl, -C(=O)R 21 , and -NHC(=O)R 22 wherein each -(C 1~5 alkylene) independently represents 1 to 5 halogenated and / or 1 to 3 unsubstituted -(C 1~3 It may be substituted with alkyl.

[0102] In some embodiments of Formula I, each R 7 are independently halide, unsubstituted -(C 1~5 alkyl), unsubstituted -(C 2~5 alkenyl), unsubstituted -(C 2~5 alkynyl), unsubstituted -(C 1~5 haloalkyl), -N(R 13 )2, -(C 1~2 Alkylene) p OR 14 , 1 to 2 R 15 may be substituted with -(C 1~2 Alkylene) p Heterocyclyl, -C(=O)R 21 , and -NHC(=O)R 22 wherein each -(C 1~2 Alkylene) may be independently substituted with 1 to 2 halides.

[0103] In some embodiments of Formula I, each R 8 are independently H, unsubstituted -(C1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0104] In some embodiments of Formula I, each R 9 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0105] In some embodiments of Formula I, each R 10 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0106] In some embodiments of Formula I, each R 11 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), 1 to 12 (e.g. 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 16 may be substituted with -(C 1~5 Alkylene) p Carbocyclyl, 1-10 (e.g. 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 1) R 17 -heterocyclyl, and 1 to 10 (e.g., 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 18-heteroaryl, optionally substituted with -(C 1~5 Alkylene) is substituted with 1-5 (e.g. 1-4, 1-3, 1-2, 1) halides (e.g. F, Cl, Br, I) and / or 1-3 (e.g. 1-2, 1) unsubstituted -(C 1~3 It may be substituted with alkyl.

[0107] In some embodiments of Formula I, each R 12 is 1 to 10 (e.g. 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 17 and optionally substituted -heterocyclyl.

[0108] In some embodiments of Formula I, each R 13 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0109] In some embodiments of Formula I, each R 14 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0110] In some embodiments of Formula I, each R 14 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -(C 1~5 Alkylene) p OR 20 is selected from the group consisting of:

[0111] In some embodiments of Formula I, each R 15 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0112] In some embodiments of Formula I, two R 15 together form a carbonyl group.

[0113] In some embodiments of Formula I, each R 16 are independently selected from halides (e.g., F, Cl, Br, I), -OMe, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0114] In some embodiments of Formula I, each R 17 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0115] In some embodiments of Formula I, each R 18 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0116] In some embodiments of Formula I, each R 19are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0117] In some embodiments of Formula I, each R 20 are independently H, unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0118] In some embodiments of Formula I, each R 21 are independently 1 to 10 (e.g. 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 17 -heterocyclyl, -N(R 11 )2, and -OR 20 is selected from the group consisting of:

[0119] In some embodiments of Formula I, each R 22 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0120] In some embodiments of Formula I, each R 22 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and -(C 1~5 Alkylene) p OR 20 is selected from the group consisting of:

[0121] In some embodiments of Formula I, each R 23 are independently unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), unsubstituted -(C 1~9 haloalkyl), and 1 to 12 (e.g., 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 1) R 24 -carbocyclyl, optionally substituted with

[0122] In some embodiments of Formula I, each R 24 are independently halides (e.g., F, Cl, Br, I), unsubstituted -(C 1~9 alkyl), unsubstituted -(C 2~9 alkenyl), unsubstituted -(C 2~9 alkynyl), and unsubstituted -(C 1~9 haloalkyl).

[0123] In some embodiments of Formula I, each p is independently 0 or 1.

[0124] In some embodiments of Formula I, each H atom is independently 2 It may be replaced by H(D) (deuterium).

[0125] Exemplary compounds of Formula I are shown in Table 1.

[0126] [Table 1] TIFF2024539620000016.tif226166TIFF2024539620000017.tif220166TIFF2024539620000018.tif208166TIFF2024539620000019.tif215166TIFF2024539620000020.tif205166TIFF2024539620000021.tif205166TIFF2024539620000022.tif201166TIFF2024539620000023.tif203166TIFF2024539620000024.tif221166TIFF2024539620000025.tif219166TIFF2024539620000026.tif227166TIFF2024539620000027.tif220166TIFF2024539620000028.tif222166TIFF2024539620000029.tif227166TIFF2024539620000030.tif220166TIFF2024539620000031.tif222166TIFF2024539620000032.tif202166TIFF2024539620000033.tif219166TIFF2024539620000034.tif220166TIFF2024539620000035.tif227166TIFF2024539620000036.tif219166TIFF2024539620000037.tif228166TIFF2024539620000038.tif225166TIFF2024539620000039.tif217166TIFF2024539620000040.tif217166TIFF2024539620000041.tif227166TIFF2024539620000042.tif219166TIFF2024539620000043.tif217166TIFF2024539620000044.tif224166TIFF2024539620000045.tif201166TIFF2024539620000046.tif228166TIFF2024539620000047.tif228166TIFF2024539620000048.tif226166TIFF2024539620000049.tif219166TIFF2024539620000050.tif217166TIFF2024539620000051.tif222166TIFF2024539620000052.tif225166TIFF2024539620000053.tif217166TIFF2024539620000054.tif218166TIFF2024539620000055.tif226166TIFF2024539620000056.tif222166TIFF2024539620000057.tif224166TIFF2024539620000058.tif226166TIFF2024539620000059.tif219166TIFF2024539620000060.tif217166TIFF2024539620000061.tif221166TIFF2024539620000062.tif226166TIFF2024539620000063.tif217166TIFF2024539620000064.tif217166TIFF2024539620000065.tif202166TIFF2024539620000066.tif197166TIFF2024539620000067.tif228166TIFF2024539620000068.tif228166TIFF2024539620000069.tif223166TIFF2024539620000070.tif217166TIFF2024539620000071.tif217166TIFF2024539620000072.tif212166TIFF2024539620000073.tif202166TIFF2024539620000074.tif228166TIFF2024539620000075.tif206166TIFF2024539620000076.tif202166TIFF2024539620000077.tif229166TIFF2024539620000078.tif203166TIFF2024539620000079.tif206166TIFF2024539620000080.tif229166TIFF2024539620000081.tif203166TIFF2024539620000082.tif212166TIFF2024539620000083.tif202166TIFF2024539620000084.tif202166TIFF2024539620000085.tif207166TIFF2024539620000086.tif202166TIFF2024539620000087.tif229166TIFF2024539620000088.tif204166TIFF2024539620000089.tif205166TIFF2024539620000090.tif229166TIFF2024539620000091.tif204166TIFF2024539620000092.tif208166TIFF2024539620000093.tif229166TIFF2024539620000094.tif206166TIFF2024539620000095.tif212166TIFF2024539620000096.tif218166TIFF2024539620000097.tif218166TIFF2024539620000098.tif215166TIFF2024539620000099.tif216166TIFF2024539620000100.tif219166TIFF2024539620000101.tif202166TIFF2024539620000102.tif202166TIFF2024539620000103.tif203166TIFF2024539620000104.tif197166TIFF2024539620000105.tif207166TIFF2024539620000106.tif197166TIFF2024539620000107.tif202166TIFF2024539620000108.tif197166TIFF2024539620000109.tif94166.

[0127] Administration and Pharmaceutical Compositions Some embodiments include a pharmaceutical composition comprising: (a) a therapeutically effective amount of a compound provided herein, or its corresponding enantiomer, diastereoisomer, or tautomer, or a pharma- ceutically acceptable salt; and (b) a pharma- ceutically acceptable carrier.

[0128] The compounds provided herein may also be useful in combination (administered simultaneously or sequentially) with other known agents.

[0129] Non-limiting examples of diseases treatable by the combination of the compound of formula (I) and another active agent include colorectal cancer, ovarian cancer, hepatocellular carcinoma, squamous cell carcinoma of the head and neck, acute lymphoblastic leukemia (ALL), pancreatic cancer, brain tumor, acute megakaryoblastic leukemia (AMKL) and osteoarthritis.For example, the compound of formula (I) can be combined with one or more chemotherapy compounds.

[0130] In some embodiments, hepatocellular carcinoma may be treated with a combination of a compound of Formula (I) and one or more of the following drugs / treatments: sorafenib (Nexavar®); regorafenib (Stivarga®, Regonix®), nivolumab (Opdivo®); lenvatinib (Lenvima®); pembrolizumab (Keytruda®); cabozantinib (Cometriq®, Cabometyx®); 5-fluorouracil (5-FU®); ramucirumab (Cyramza®); gemcitabine and oxaliplatin (GEMOX). Other treatments that may be feasible in combination with the compounds of formula (I) include i) transcatheter arterial chemoembolization (TACE) in combination with doxorubicin (DOXIL®), cisplatin, or mitomycin C (Mitosol®, Mutamycin®, Jelmyto®); ii) low dose rate brachytherapy.

[0131] In some embodiments, head and neck squamous cell carcinoma can be treated with a combination of a compound of formula (I) and one or more of the following drugs / treatments: transoral robotic assisted surgery (TORS); TORS in combination with radiation therapy; latrolectinib (Vitrakvi®); EGFR inhibitors such as erlotinib (Tarceva®), osimertinib (Tagrisso®), neratinib (Nerlynx®), gefitinib (Iressa®), cetuximab (Erbitux®), panitumumab (Vectibix®), dacomitinib (Vizimpro®), lapatinib (Tykerb®), necitumumab (Portrazza), and vandetanib (Caprelsa®).

[0132] In some embodiments, acute lymphoblastic leukemia (ALL) can be treated with a combination of a compound of formula (I) and one or more of the following drugs / treatments: induction therapy; consolidation therapy; nelarabine (Arranon®); blackleg asparaginase (Erwinaze®); blackleg asparaginase (recombinant)-rywn (Rylaze®); calaspargase pegol-mknl (Asparlas®); inotuzumab ozogamicin (Besponsa®); blinatumomab (Blincyto®); daunorubicin hydrochloride (Cerubidine®); clofarabine (Clolar®); cyclophosphamide; methotrexate sodium (Trexall®); cytarabine (Cytosar-U®); dasatinib (Sprycel®); Dexamethasone; imatinib mesylate (Gleevec®); ponatinib hydrochloride (Iclusig®); mercaptopurine (Purinethol®, Purixan®); tisagenlecleucel (Kymriah®); vincristine sulfate liposomal (Marqibo®); pegaspargase (Oncaspar®); prednisone; daunorubicin hydrochloride (Rubidomycin®); and vincristine sulfate.

[0133] In some embodiments, pancreatic cancer may be treated with a combination of a compound of Formula (I) and one or more of the following drugs / treatments: ablation and embolization treatments; gemcitabine (Gemzar®); 5-fluorouracil (5-FU®); oxaliplatin (Eloxatin®); albumin-bound paclitaxel (Abraxane®); capecitabine (Xeloda®); cisplatin; irinotecan (Camptosar®); liposomal irinotecan (Onivyde®); paclitaxel (Taxol®), and docetaxel (Taxotere®).

[0134] In some embodiments, brain tumors can be treated by a combination of a compound of formula (I) and one or more of the following drugs / treatments: carmustine can be administered by Gliadel wafer; in glioblastoma and high-grade gliomas, radiation therapy combined with daily low-dose temozolomide (Temodar®) followed by monthly temozolomide for 6 months to 1 year after radiation therapy; lomustine (Gleostine®), procarbazine (Matulane®), and vincristine (Vincasar®) have been used in conjunction with radiation therapy; antiangiogenic treatment with bevacizumab (Avastin®, Mvasi®); and targeted treatment using latrolectinib (Vitrakvi®).

[0135] In some embodiments, acute megakaryoblastic leukemia (AMKL) can be treated with a combination of a compound of formula (I) and one or more of the following drugs / treatments: cytarabine (Cytosar-U®), etoposide (Vepesid®), and anthracycline drugs. Anthracyclines include daunorubicin (Cerubidine®), idarubicin (Idamycin®), and mitoxantrone (Novantrone®).

[0136] In some embodiments, acute myeloid leukemia (AML) can be treated with a combination of a compound of Formula (I) and one or more of the following drugs / treatments: venetoclax and a hypomethylating agent (e.g., decitabine, azacitidine), induction chemotherapy (cytarabine and an anthracycline (e.g., daunorubicin or idarubicin), all-trans retinoic acid (ATRA) and either arsenic trioxide (ATO) monotherapy or an anthracycline), consolidation therapy (cytarabine).

[0137] In some embodiments, myelodysplastic syndromes (MDS) can be treated with a combination of a compound of formula (I) and one or more of the following drugs / treatments: 5-azacytidine, decitabine, lenalidomide, and decitabine / cedazuridine (Inqovi®).

[0138] In some embodiments, colorectal cancer can be treated by a combination of the compound of formula (I) with one or more of the following drugs: 5-fluorouracil (5-FU), which can be administered with the vitamin-like drug leucovorin (also called folinic acid); capecitabine (XELODA®), irinotecan (CAMPOSTAR®), oxaliplatin (ELOXATIN®). Examples of these drug combinations that can be further combined with the compound of formula (I) include FOLFOX (5-FU, leucovorin, and oxaliplatin), FOLFIRI (5-FU, leucovorin, and irinotecan), FOLFOXIRI (leucovorin, 5-FU, oxaliplatin, and irinotecan), and CapeOx (capecitabine and oxaliplatin). For rectal cancer, chemotherapy with 5-FU or capecitabine may be given in combination with radiation therapy before surgery (neoadjuvant therapy).

[0139] In some embodiments, ovarian cancer can be treated with a combination of a compound of Formula (I) and one or more of the following drugs: topotecan, liposomal doxorubicin (DOXIL®), gemcitabine (GEMZAR®), cyclophosphamide (CYTOXAN®), vinorelbine (NAVELBINE®), ifosfamide (IFEX®), etoposide (VP-16), altretamine (HEXALEN®), capecitabine (XELODA®), irinotecan (CPT-11, CAMPTOSAR®), melphalan, pemetrexed (ALIMTA®), and albumin-bound paclitaxel (nab-paclitaxel, ABRAXANE®). Examples of these drug combinations that can be further combined with the compound of formula (I) include TIP (paclitaxel [Taxol], ifosfamide, and cisplatin), VeIP (vinblastine, ifosfamide, and cisplatin), and VIP (etoposide [VP-16], ifosfamide, and cisplatin). Ovarian cancer can also be treated by combining the compound of formula (I) with immune checkpoint blockade (ICB) therapy.

[0140] In some embodiments, the compounds of formula (I) can be used in combination with any of the following methods to treat cancer: (a) hormonal therapy, such as aromatase inhibitors, LHRH [luteinizing hormone releasing hormone] analogs and inhibitors; (b) ablation or embolization procedures, such as radiofrequency ablation (RFA), ethanol (alcohol) ablation, microwave thermotherapy, and cryosurgery (cryotherapy); (c) chemotherapy using alkylating agents, such as cisplatin and carboplatin, oxaliplatin, mechlorethamine, cyclophosphamide, chlorambucil, and ifosfamide; (d) chemotherapy using antimetabolites, such as azathioprine and mercaptopurine; (e) chemotherapy using plant alkaloids and plant terpenoids, such as the vinca alkaloids (i.e. vincristine, vinblastine, vinorelbine, and vindesine), and taxanes; (f) chemotherapy using terpenoids, such as ... (g) chemotherapy using topoisomerase inhibitors, such as irinotecan, topotecan, amsacrine, etoposide, etoposide phosphate, and teniposide; (h) chemotherapy using cytotoxic antibiotics, such as actinomycin, anthracyclines, doxorubicin, daunorubicin, valrubicin, idarubicin, epirubicin, bleomycin, plicamycin, and mitomycin;(i) tyrosine kinase inhibitors, such as imatinib mesylate (GLEEVEC®, also known as STI-571), gefitinib (Iressa, also known as ZD1839), erlotinib (sold as TARCEVA®), bortezomib (VELCADE®), tamoxifen, tofacitinib, crizotinib, Bcl-2 inhibitors (e.g. obatoclax, navitoclax (ABT-263), oblimersen (G3139), venetoclax (ABT-199), gossypii (G2010), cefotiamide (CE ... chemotherapy using Pall), PARP inhibitors (e.g., iniparib, olaparib, rucaparib, niraparib, talazoparib), PI3K inhibitors (e.g., perifosine, which is in Phase III trials), VEGF receptor 2 inhibitors (e.g., apatinib), AN-152 (AEZS-108), Braf inhibitors (e.g., vemurafenib, dabrafenib, and LGX818), MEK inhibitors (e.g., trametinib and MEK162), CDK inhibitors (e.g., PD-0332991), salinomycin, and sorafenib; (j) chemotherapy using monoclonal antibodies, such as rituximab (sold as MABTHERA® or RITUXAN®), trastuzumab (Herceptin, also known as ErbB2), cetuximab (sold as ERBITUX®), and bevacizumab (sold as AVASTIN®); (k) chemotherapy using KRAS G12C inhibitors, such as sotorasib (Lumakras® and Lumykras®), adagrasib (MRTX849), and ARS-3248 (Wellspring Biosciences); (l) Chemotherapy using checkpoint inhibitor therapy, such as ipilimumab (Yervoy®), nivolumab (Opdivo®), pembrolizumab (Keytruda®), atezolizumab (Tecentriq®), avelumab (Bavencio), durvalumab (Imfinzi), cemiplimab (Libtayo®), and spartalizumab (PDR001);(m) chemotherapy using antibody-drug conjugates (ADCs), such as gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab emtansine, inotuzumab ozogamicin, polatuzumab vedotin, enfortumab vedotin, trastuzumab deruxtecan, sacituzumab govitecan, belantamab mafodotin, moxetumomab pasudotox, and loncastuximab tesirine; (n) Chemotherapy using proteasome inhibitors such as carfilzomib, lactacystin, disulfiram, salinosporamide A (marizomib), oprozomib, delanzomib, epoxomicin, MG132, β-hydroxyβ-methylbutyrate (HMB), bortezomib, ixazomib (alone or in combination with lenalidomide and dexamethasone); and (o) radiation therapy.

[0141] In some embodiments, compounds of formula I can be used in combination with any of the following methods to treat diabetes: (a) insulin injections; (b) biguanides, such as metformin (Glucophage), phenformin (DBI), and buformin; (c) thiazolidinediones (TZDs), such as rosiglitazone (Avandia), pioglitazone (Actos), and troglitazone (yroglitazone) (Rezulin); (d) lyn kinase activators, such as glimepiride (Amaryl®) and tolumidone (MLR-1023); (e) Secretagogues, such as sulfonylureas (non-limiting examples include acetohexamide, carbutamide, chlorpropamide, glyciclamide (tolcyclamide), metahexamide, tolazamide, tolbutamide, glibenclamide (glyburide), glibornuride, gliclazide, glipizide, gliquidone, glisoxepide, glyclopyramide, and glimepiride) and meglitinides (non-limiting examples include repaglinide (Prandin), nateglinide (Starlix), and mitiglinide (Glufast)); (f) α-glucosidase inhibitors, such as acarbose (Glucobay, Precose, Prandase), miglitol (Glyset), and voglibose; (g) Injectable incretin mimetics, such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (glucose-dependent insulinotropic peptide, GIP).Non-limiting examples of injectable glucagon-like peptide (GLP) analogs and agonists include exenatide (Exendin-4, sold as Byetta), liraglutide (Victoza, Saxenda), taspoglutide, lixisenatide (Lyxumia), semaglutide (Ozempic, Rybelsus), dulaglutide (Trulicity), and albiglutide (Tanzeum); non-limiting examples of dipeptidyl peptidase-4 (DPP-4) inhibitors include sitagliptin (Januvia), vildagliptin (Galvus), and saxagliptin. gliptin (Onglyza), linagliptin (Tradjenta), gemigliptin (Zemiglo), anagliptin (Suiny), teneligliptin (Tenelia), alogliptin (Nesina, Vipidia, Kazano, Vipidomet (combined with metformin), Oseni, Incresync (combined with pioglitazone)), trelagliptin (Zafatek, Wedica), omarigliptin (MK-3102), evogliptin (Suganon, Evodine), gosogliptin (Saterex), and dutogliptin; (h) injectable amylin analogues, such as pramlintide (Symlin); (i) glucotropic drugs (SGLT2 inhibitors), such as canagliflozin (Invokana, Sulisent, Prominad), dapagliflozin (Forxiga, Farxiga, Edistride), empagliflozin (Jardiance, Sciampa-M), ertugliflozin (Steglatro), ipragliflozin (Suglat), luseogliflozin (Lusefi), remogliflozin etabonate (prodrug of remogliflozin), sergliflozin etabonate (GW869682X), sotagliflozin (Zynquista), and tofogliflozin (CSG452).

[0142] In some embodiments, the compounds of formula (I) can be used in combination with any of the following methods to treat osteoarthritis: (d) injections of Wnt signaling pathway inhibitors (e.g., Loresivivint); (a) nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, aspirin, and acetaminophen; (b) physical therapy; (c) injections of corticosteroids; (d) injections of hyaluronic acid derivatives (e.g., Hyalgan, Synvisc); (e) narcotics such as codeine; (f) braces and / or shoe inserts, or any device capable of immobilizing or supporting a joint so that pressure is not placed on the joint (e.g., splints, braces, shoe inserts, or other medical devices); (g) bone realignment (osteotomy); (h) joint replacement (arthroplasty); and (i) chronic pain classes.

[0143] In some embodiments, the compounds of formula (I) can be used in combination with aducanumab (Aduhelm™); acetylcholinesterase inhibitors such as tacrine, rivastigmine (Exelon®), galantamine (Razadyne® and GalantaMind™), and donepezil (Aricept®); and memantine (Axura®, Ebixa®, Namenda®) to treat Alzheimer's disease.

[0144] Administration of the compounds disclosed herein or pharma- ceutically acceptable salts thereof may be by any of the accepted modes of administration, including, but not limited to, oral, subcutaneous, intravenous, intranasal, topical, transdermal, intraperitoneally, intramuscular, intrapulmonary, vaginal, rectal, otological, neuro-otological, intraocular, subconjunctival, anterior chamber injection, intravitreal, intraperitoneal, intrathecal, intracystic, intrapleural, wound irrigation, buccal, intra-abdominally, intra-articular, intra-auricular, intrabronchial, intracapsular, intrameningeal, inhalation, intratracheal or intrabronchial injection, direct injection into pulmonary cavities, intraspinal, intra-articular bursa, intrathoracic, thoracic fistula irrigation, epidural, intratympanic, intracisternal, intravascular, intraventricular, intraosseous, irrigation of infected bone, or application as part of any admixture with a prosthesis. In some embodiments, the method of administration comprises oral or parenteral administration.

[0145] The compounds provided herein intended for pharmaceutical use can be administered as crystalline or amorphous products. Pharmaceutically acceptable compositions can include solids, semisolids, liquids, solutions, colloids, liposomes, emulsions, suspensions, complexes, coacervates, and aerosols. Dosage forms can include, for example, tablets, capsules, powders, liquids, suspensions, suppositories, aerosols, implantable tablets, controlled release dosage forms, and the like. Dosage forms can be obtained, for example, as solid plugs, powders, or films, by methods such as precipitation, crystallization, pulverization, grinding, supercritical fluid processing, coacervation, complex coacervation, encapsulation, emulsification, complex formation, freeze drying, spray drying, or evaporative drying. Microwave or radio frequency drying can be used for this purpose. The compounds may also be administered in sustained or controlled release dosage forms including depot injections, osmotic pumps, pills (tablets and / or capsules), transdermal patches (including electrotransport patches), implantable tablets, and the like, for extended and / or timed pulse administration at a predetermined rate.

[0146] The compounds can be administered alone or in combination with conventional pharmaceutical carriers, excipients, etc. Pharmaceutically acceptable excipients include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS) such as d-α-tocopherol polyethylene glycol 1000 succinate, surfactants used in pharmaceutical dosage forms such as Tween, poloxamer, or other similar polymeric delivery matrices, serum proteins such as human serum albumin, buffer substances such as phosphates, Tris, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, protamine sulfate, salts or electrolytes such as disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulosic substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene block copolymers, and wool fat. Also, chemically modified derivatives such as cyclodextrins, such as α-, β-, and γ-cyclodextrin, or hydroxyalkyl cyclodextrins, including 2- and 3-hydroxypropyl-β-cyclodextrin, or other solubilizing derivatives, can be used to enhance delivery of the compounds described herein. Dosage forms or compositions can be prepared that contain the compounds described herein in the range of 0.005%-100%, with the remainder consisting of a non-toxic carrier. Contemplated compositions can contain 0.001%-100%, in one embodiment 0.1-95%, in another embodiment 75-85%, and in a further embodiment 20-80% of the compounds provided herein. Actual methods for preparing these dosage forms will be known or apparent to those of skill in the art. For example, see Remington: The Science and Practice of Pharmacy, 22 nd Edition (Pharmaceutical Press, London, UK. 2012).

[0147] In one embodiment, the composition is in the form of a unitary dosage form such as a pill or tablet, and thus the composition may comprise, together with the compound provided herein, a diluent such as lactose, sucrose, dicalcium phosphate; a lubricant such as magnesium stearate; and a binder such as starch, gum arabic, polyvinylpyrrolidine, gelatin, cellulose, cellulose derivatives.In another solid dosage form, a powder, marume, solution or suspension (e.g. in propylene carbonate, vegetable oil, PEG, poloxamer 124, or triglyceride) is enclosed in a capsule (gelatin or cellulose-based capsule).A unitary dosage form in which one or more compounds provided herein or additional active agents are physically separated is also envisioned, such as a capsule with granules (or tablets in capsules) of each drug; a two-layer tablet; a two-compartment gel capsule, etc.An enteric-coated oral dosage form or delayed release oral dosage form is also envisioned.

[0148] Pharmaceutically administrable liquid compositions can be prepared, for example, by dissolving, dispersing, etc., a compound provided herein and optional pharmaceutical excipients in a carrier (e.g., water, saline, aqueous dextrose, glycerin, glycol, ethanol, etc.) to form a solution, colloid, liposome, emulsion, complex, coacervate, or suspension. If desired, the pharmaceutical compositions may contain minor amounts of nontoxic auxiliary substances such as wetting agents, emulsifying agents, cosolvents, solubilizing agents, pH buffering agents, and the like (e.g., sodium acetate, sodium citrate, cyclodextrin derivatives, sorbitan monolaurate, triethanolamine acetate, triethanolamine oleate, and the like).

[0149] In some embodiments, the unit dosage of the compound of formula (I) is from about 0.25 mg / Kg to about 50 mg / Kg in humans.

[0150] In some embodiments, the unit dosage of the compound of formula (I) is from about 0.25 mg / Kg to about 20 mg / Kg in humans.

[0151] In some embodiments, the unit dosage of the compound of formula (I) is from about 0.50 mg / Kg to about 19 mg / Kg in humans.

[0152] In some embodiments, the unit dosage of the compound of formula (I) is from about 0.75 mg / Kg to about 18 mg / Kg in humans.

[0153] In some embodiments, the unit dosage of the compound of formula (I) is from about 1.0 mg / Kg to about 17 mg / Kg in humans.

[0154] In some embodiments, the unit dosage of the compound of formula (I) is from about 1.25 mg / Kg to about 16 mg / Kg in humans.

[0155] In some embodiments, the unit dosage of the compound of formula (I) is from about 1.50 mg / Kg to about 15 mg / Kg in humans.

[0156] In some embodiments, the unit dosage of the compound of formula (I) is from about 1.75 mg / Kg to about 14 mg / Kg in humans.

[0157] In some embodiments, the unit dosage of the compound of formula (I) is from about 2.0 mg / Kg to about 13 mg / Kg in humans.

[0158] In some embodiments, the unit dosage of the compound of formula (I) is from about 3.0 mg / Kg to about 12 mg / Kg in humans.

[0159] In some embodiments, the unit dosage of the compound of formula (I) is from about 4.0 mg / Kg to about 11 mg / Kg in humans.

[0160] In some embodiments, the unit dosage of the compound of formula (I) is from about 5.0 mg / Kg to about 10 mg / Kg in humans.

[0161] In some embodiments, the compositions are provided in a unit dosage form suitable for single administration.

[0162] In some embodiments, the composition is provided in a unit dosage form suitable for twice-daily administration.

[0163] In some embodiments, the composition is provided in a unit dosage form suitable for administration three times daily.

[0164] Injectable solutions can be prepared in conventional forms, as solutions, colloids, liposomes, complexes, coacervates, or suspensions, as emulsions, or in solid forms suitable for reconstitution in liquid prior to injection.The percentage of the compounds provided herein contained in these parenteral compositions depends largely on their specific nature, as well as the activity of the compounds and the needs of the patient.However, percentages of active ingredient of 0.01% to 10% in solution can be used.This percentage can be higher if the composition is a solid or suspension, which can then be diluted to the above percentages.

[0165] In some embodiments, the compositions contain about 0.1-10% of the active agent in solution.

[0166] In some embodiments, the compositions contain about 0.1-5% of the active agent in solution.

[0167] In some embodiments, the compositions contain about 0.1-4% of the active agent in solution.

[0168] In some embodiments, the compositions contain about 0.15-3% of the active agent in solution.

[0169] In some embodiments, the composition contains about 0.2-2% of the active agent in solution.

[0170] In some embodiments, the composition is provided in a form suitable for continuous administration by intravenous infusion over a period of about 1 to 96 hours.

[0171] In some embodiments, the composition is provided in a form suitable for continuous administration by intravenous infusion over a period of about 1 to 72 hours.

[0172] In some embodiments, the composition is provided in a form suitable for continuous administration by intravenous infusion over a period of about 1 to 48 hours.

[0173] In some embodiments, the compositions are provided in a form suitable for continuous administration by intravenous infusion over a period of about 1 to 24 hours.

[0174] In some embodiments, the composition is provided in a form suitable for continuous administration by intravenous infusion over a period of about 1 to 12 hours.

[0175] In some embodiments, the composition is provided in a form suitable for continuous administration by intravenous infusion over a period of about 1 to 6 hours.

[0176] In some embodiments, these compositions are administered by intravenous infusion at a dose of about 5 mg / m 2 ~about 300mg / m 2 can be administered to a human at a dose of

[0177] In some embodiments, these compositions are administered by intravenous infusion at a dose of about 5 mg / m 2 ~about 200mg / m 2 can be administered to a human at a dose of

[0178] In some embodiments, these compositions are administered by intravenous infusion at a dose of about 5 mg / m 2 ~about 100mg / m 2 can be administered to a human at a dose of

[0179] In some embodiments, these compositions are administered by intravenous infusion at a dose of about 10 mg / m 2 ~about 50mg / m 2 can be administered to a human at a dose of

[0180] In some embodiments, these compositions are administered by intravenous infusion at about 50 mg / m 2 ~about 200mg / m 2 can be administered to a human at a dose of

[0181] In some embodiments, these compositions are administered by intravenous infusion at about 75 mg / m 2 ~about 175mg / m 2 can be administered to a human at a dose of

[0182] In some embodiments, these compositions are administered by intravenous infusion at a dose of about 100 mg / m 2 ~about 150mg / m 2 can be administered to a human at a dose of

[0183] It should also be noted that concentration and dosage values ​​may vary depending on the specific compound and the severity of the condition to be alleviated.It should further be understood that for any specific patient, specific dosage regimen should be adjusted over time according to individual needs and the professional judgment of the person administering or supervising the administration of the composition, and that the concentration ranges described herein are merely exemplary and are not intended to limit the scope or practice of the claimed compositions.

[0184] In one aspect, the compositions can be administered to the respiratory tract (including the nose and lungs) via, for example, a nebulizer, a metered dose inhaler, an atomizer, a mister, an aerosol, a dry powder inhaler, a gas insufflator, liquid drops, or other suitable device or technique.

[0185] In some embodiments, aerosols intended for delivery to the nasal mucosa are provided for inhalation through the nose. For optimal delivery to the nasal cavity, an inhaled particle size of about 5 to about 100 microns is useful, with a particle size of about 10 to about 60 microns being preferred. For nasal delivery, larger inhaled particle sizes may be desirable to maximize impaction on the nasal mucosa and minimize or prevent pulmonary deposition of the administered formulation. In some embodiments, aerosols intended for delivery to the lungs are provided for inhalation through the nose or mouth. For pulmonary delivery, an aerodynamic inhaled particle size of less than about 10 μm is useful (e.g., about 1 to about 10 microns). Inhaled particles may be defined as droplets containing dissolved drug, droplets containing suspended drug particles (when the drug is insoluble in the suspending medium), dry particles of pure drug substance, drug substance with incorporated excipients, liposomes, emulsions, colloidal systems, coacervates, aggregates of drug nanoparticles, or dry particles of a diluent containing embedded drug nanoparticles.

[0186] In some embodiments, the compounds of formula (I) disclosed herein intended for respiratory delivery (systemic or local) can be administered as aqueous formulations, non-aqueous solutions or suspensions, suspensions or solutions in halogenated hydrocarbon propellants with or without alcohol, colloidal systems, emulsions, coacervates, or dry powders. Aqueous formulations can be aerosolized by liquid nebulizers using hydraulic or ultrasonic atomization, or by modified micropump systems (such as soft mist inhalers, Aerodose®, or AERx® systems). Propellant-based systems can utilize suitable pressurized metered dose inhalers (pMDIs). Dry powders can utilize dry powder inhalers (DPIs) that can effectively disperse the drug substance. The desired particle size and particle size distribution can be obtained by selecting the appropriate device.

[0187] In some embodiments, the compositions of formula (I) disclosed herein can be administered to the ear in a variety of ways, for example, using a round window catheter (e.g., U.S. Patent Nos. 6,440,102 and 6,648,873).

[0188] Alternatively, the formulations can be incorporated into a wick used between the outer and middle ear (e.g., U.S. Patent No. 6,120,484) or absorbed onto a collagen sponge or other solid support (e.g., U.S. Patent No. 4,164,559).

[0189] If desired, the formulations of the present disclosure can be incorporated into gel formulations (eg, US Pat. Nos. 4,474,752 and 6,911,211).

[0190] In some embodiments, compounds of formula (I) disclosed herein intended for delivery to the ear can be administered via an implanted pump and delivery system, through a needle directly into the middle or inner ear (cochlea), or through an alternatively provided drug delivery channel, such as, but not limited to, a cochlear implant stylet electrode channel, or a needle through the temporal bone into the cochlea.

[0191] Other options include delivery via a pump through a thin film coated onto a multi-channel electrode, or onto an electrode with specially implanted drug delivery channels (pathways) engraved into the film for this purpose. In other embodiments, the solid acidic or basic compounds of formula (I) can be delivered from the reservoir of an externally or internally implanted pumping system.

[0192] The formulations of the present disclosure can also be administered to the ear by intratympanic injection into the middle ear, inner ear, or cochlea (e.g., U.S. Patent No. 6,377,849 and U.S. Patent Application No. 11 / 337,815).

[0193] Intratympanic injection of therapeutic agents is a technique of injecting therapeutic agents into the middle and / or inner ear behind the tympanic membrane.In one embodiment, the formulations described herein are administered directly onto the round window membrane via transtympanic injection.In another embodiment, the auris-acceptable ion channel modulating agent formulations described herein are administered onto the round window membrane via a non-transtympanic approach to the inner ear.In a further embodiment, the formulations described herein are administered onto the round window membrane via a surgical approach to the round window membrane, including modification of the crista fenestrae.

[0194] In some embodiments, the compounds of formula (I) are formulated into rectal compositions such as enemas, rectal gels, rectal foams, rectal aerosols, suppositories, jelly suppositories, or retention enemas containing conventional suppository bases such as cocoa butter or other glycerides, and synthetic polymers such as polyvinylpyrrolidone, PEG (such as PEG ointment), and the like.

[0195] Suppositories for rectal administration of drugs (as a solution, colloid, suspension, or complex) can be prepared by mixing the compounds provided herein with suitable non-irritating excipients that are solid at normal temperatures but liquid at rectal temperatures, and thus melt or erode / dissolve in the rectum to release the compounds.These materials include cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, poloxamer, mixtures of polyethylene glycols of various molecular weights, and polyethylene glycol fatty acid esters.In the suppository form of the composition, a low melting wax, such as but not limited to a mixture of fatty acid glycerides, optionally in combination with cocoa butter, is melted first.

[0196] Solid composition can be provided in various different types of dosage forms based on the physicochemical properties of the compound provided herein, the desired dissolution rate, cost considerations, and other criteria.In one embodiment, solid composition is a single unit.This implies that a single unit dose of the compound is contained in a single physically shaped solid form or article.In other words, solid composition is cohesive, which is in contrast to the multiple unit dosage form, in which the unit is non-cohesive.

[0197] The example of one unit that can be used as the dosage form of the solid composition includes tablets such as compressed tablets, film units, foil units, oblates, freeze-dried matrix units, etc. In one embodiment, the solid composition is a highly porous freeze-dried form.These freeze-dried products, sometimes also called oblates or freeze-dried tablets, are particularly useful for rapid disintegration, which also allows the compound to dissolve quickly.

[0198] On the other hand, in some applications, the solid composition may be formed as a multiple unit dosage form as defined above. Examples of multiple units include powder, granule, microparticle, pellet, mini tablet, bead, freeze-dried powder, etc. In one embodiment, the solid composition is a freeze-dried powder. This dispersion freeze-dried system includes a large number of powder particles, and due to the freeze-drying process used to form the powder, each particle has an irregular and porous microstructure through which the powder can absorb water very quickly, resulting in rapid dissolution. It is also assumed that the effervescent composition promotes the rapid dispersion and absorption of the compound.

[0199] Another type of multiparticulate system that can also achieve rapid drug dissolution is the multiparticulate system of powder, granule or pellet from water-soluble excipients coated with the compound provided herein, so that the compound is located on the outer surface of each particle.In this type of system, water-soluble low molecular weight excipients can be useful for preparing the core of these coated particles, and then these coated particles can be coated with a coating composition that includes the compound and one or more additional excipients, such as binders, pore formers, sugars, sugar alcohols, film-forming polymers, plasticizers, or other excipients used in pharmaceutical coating compositions.

[0200] Also provided herein is a kit. Typically, the kit comprises one or more compounds or compositions described herein. In certain embodiments, the kit can comprise one or more delivery systems, for example, for delivering or administering the compounds provided herein, and instructions for using the kit (e.g., instructions for treating a patient). In another embodiment, the kit can comprise the compounds or compositions described herein and a label indicating that the contents should be administered to a patient with cancer. In another embodiment, the kit may comprise a compound or composition as described herein and a label indicating that the contents should be administered to a patient having one or more of glioblastoma, ovarian cancer, breast cancer, pancreatic cancer, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, chronic myeloid leukemia, Alzheimer's disease, amyotrophic lateral sclerosis, CDKL5 deficiency disorder, Down's syndrome, frontotemporal dementia with parkinsonism-17 (FTDP-17), dementia with Lewy bodies, Parkinson's disease, Pick's disease, autism, dementia, epilepsy, Huntington's disease, and multiple sclerosis.

[0201] Treatment Methods The compounds and compositions provided herein can be used as DYRK1A inhibitors, and can therefore be used to treat various disorders and diseases involving overexpression of DYRK1A, such as cancer and neurological conditions / neurological disorders / neurological diseases.Non-limiting examples of diseases treatable with the compounds and compositions provided herein include various cancers, Alzheimer's disease, amyotrophic lateral sclerosis, CDKL5 deficiency disorder, Down's syndrome, frontotemporal dementia with parkinsonism-17 (FTDP-17), dementia with Lewy bodies, Parkinson's disease, Pick's disease, and additional diseases with significant neurodegeneration, such as autism, dementia, epilepsy, Huntington's disease, multiple sclerosis; Diseases and disorders associated with acquired brain injury include, for example, chronic traumatic encephalopathy, traumatic brain injury, tumors, stroke, tauopathies (e.g., Pick's disease, progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, globular glial tauopathy, primary age-related tauopathies including neurofibrillary tangle dementia, chronic traumatic encephalopathy (CTE), frontotemporal lobar degeneration with tau inclusions (FTLD-tau), and age-related tau astrogliopathy). Clinical manifestations include frontotemporal dementia, corticobasal syndrome, Richardson's syndrome, Parkinsonism, pure akinesia with freezing of gait, and rarely motor neuron symptoms or cerebellar ataxia, diabetes mellitus, psoriasis, knee osteoarthritis, tendinopathy, human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), hepatitis C virus (HCV), and herpes simplex virus type 1 (HSV-1).

[0202] The gene encoding DYRK1A is located on chromosome 21 within the Down syndrome critical region (DSCR), whose triploidy is responsible for most Down syndrome-associated defects (FEBS Journal (2011), 278, 246-256). There is substantial genetic and pharmacological evidence that a mere 1.5-fold overexpression of DYRK1A is responsible for most cognitive impairments observed in Down syndrome patients (Pharmacology & Therapeutics (2019), 194, 199-221 and Brain Science (2018), 8(10), 187). Genetic normalization of DYRK1A levels or pharmacological inhibition of its catalytic activity restores cognitive function. The development of pharmacological inhibitors of DYRK1A is a major avenue for the treatment of cognitive impairments associated with Down syndrome.

[0203] DYRK1A and DYRK1B are utilized during placental replication of human cytomegalovirus (HCMV). Inhibition of DYRKs prevents the replication of various viruses, including hepatitis C virus (HCV), human cytomegalovirus (HCMV), human immunodeficiency virus type 1 (HIV-1), and herpes simplex virus type 1 (HSV-1) (Journal of Virology (2020), 94(6) and PLoS ONE (2015), 10, e0144229).

[0204] Accumulating evidence shows that DYRK1A / 1B inhibitors induce proliferation of insulin-producing pancreatic β-cells, making DYRK1A / 1B kinases an attractive therapeutic target for β-cell regeneration in both type 1 and type 2 diabetes as well as gestational diabetes (Nature Communications (2015), 6(8372); Diabetes (2016), 65(6), 1660-1671; JCI Insight (2020), 5(1), e132594; Science Translational Medicine (2020), 12(530); International Journal of Molecular Sciences (2021), 22(16), 9083; and Journal of Medicinal Chemistry (2021), 64(6), 2901-2922). Other forms of diabetes treatable with DYRK inhibitors include maturity-onset diabetes of the young (MODY, monogenic diabetes), cases of diabetes caused by tissue receptors in the body that do not respond to insulin, double diabetes (when type 1 diabetes becomes insulin resistant), diabetes associated with excessive secretion of insulin antagonist hormones, malnutrition-related diabetes (ICD-10 code E12), and diabetes caused by any genetic mutation (autosomal or mitochondrial) that results in beta cell dysfunction.

[0205] There is a wealth of literature linking DYRK1A to solid tumors and leukemia (Pharmacology & Therapeutics (2015), 151, 87-98; Cancers (2020), 12(8), 2106; and Cellular and Molecular Life Sciences (2021), 78, 603-619). The most prominent examples are pancreatic cancer (Gut (2019), 68(8), 1465-1476 and Gene (2020), 758, 144960), brain tumors, glioblastomas (Journal of Clinical Investigation (2013), 123(6), 2475-2487), acute megakaryoblastic leukemia (AMKL) (Journal of Clinical Investigation (2012), 122(3), 948-962), and acute lymphoblastic leukemia (ALL) (Journal of Clinical Investigation (2021), 131(1), e135937). Other cancers that have been linked to DYRK1A include ovarian cancer (Frontiers in Oncology (2021), 11, 637193), head and neck squamous cell carcinoma (Scientific Reports (2016), 6, 36132), and hepatocellular carcinoma (Cell Death & Disease (2021), 12, 125), where DYRK1A regulates the DNA damage response (Scientific Reports (2019), 9, 6014 and Scientific Reports (2019), 9, 6539). In some circumstances, DYRK1A appears to function as a tumor suppressor protein (Molecular & Cellular Oncology (2015), 2(1), e970048 and Nature (2016), 529, 172-177).

[0206] Other cancers can also be treated with the compounds and compositions described herein.

[0207] More specifically, cancers treatable by the compounds, compositions, and methods described herein include, but are not limited to:

[0208] 1) ER + Breast cancer, ER - Breast cancer, her2 - Breast cancer, her2 breast cancer; stromal tumors such as fibroadenoma, phyllodes tumor, and sarcoma, as well as epithelial tumors such as large intraductal papillomas; cancer of the breast, including carcinoma in situ (non-invasive cancer), including ductal carcinoma in situ (including Paget's disease) and lobular carcinoma in situ, and invasive carcinoma (invasive cancer), including but not limited to invasive ductal carcinoma, invasive lobular carcinoma, medullary carcinoma, colloid carcinoma (mucinous carcinoma), tubular carcinoma, and invasive papillary carcinoma; breast cancer, including, for example, chemotherapy-resistant breast cancer (TNBC), as well as various malignant neoplasms. Further examples of breast cancer include luminal A, luminal B, basal A, basal B, and estrogen receptor negative (ERN) breast cancer. - ), progesterone receptor negative, and HER2 negative (HER2 - In some embodiments, the breast cancer may exhibit a high-risk Oncotype Score.

[0209] 2) Sarcomas, such as angiosarcoma, fibrosarcoma, rhabdomyosarcoma, and liposarcoma; myxoma; rhabdomyoma; fibroma; lipoma; and cardiac cancer, including, for example, teratomas.

[0210] 3) Lung cancer, including, for example, bronchogenic carcinoma, such as squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, and adenocarcinoma; alveolar carcinoma and bronchiolar carcinoma; bronchial adenoma; sarcoma; lymphoma; chondroitin hamartoma; chemotherapy-resistant small cell lung cancer (SCLC); and mesothelioma.

[0211] 4) Cancer of the esophagus, e.g. squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, and lymphoma; cancer of the stomach, e.g. carcinoma, lymphoma, and leiomyosarcoma; cancer of the pancreas, e.g. tubular adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, and vipoma; colon cancer with APC gene mutation; cancer of the small intestine, e.g. adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, and fibroma; cancer of the large intestine, e.g. gastrointestinal cancer, including, e.g., adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, and leiomyoma.

[0212] 5) Cancer of the kidney, e.g., adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, and leukemia; cancer of the bladder and urethra, e.g., squamous cell carcinoma, transitional cell carcinoma, and adenocarcinoma; cancer of the prostate, e.g., adenocarcinoma and sarcoma; genitourinary cancers, including, e.g., cancer of the testes, e.g., seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, and lipoma.

[0213] 6) Hepatocellular carcinomas, including, for example, hepatocellular carcinoma; cholangiocarcinoma; hepatoblastoma; angiosarcoma; hepatocellular adenoma; and hemangioma.

[0214] 7) Bone cancer, including, for example, osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochondroma (osteochondral exostosis), benign chondroma, chondroblastoma, chondromyxoid fibroma, osteoid osteoma, and giant cell tumor.

[0215] 8) Cancers of the skull, e.g. osteoma, hemangioma, granuloma, xanthomas, and osteitis deformans; cancers of the meninges, e.g. meningioma, meningeal sarcoma, and gliomatosis; cancers of the brain, e.g. astrocytoma, medulloblastoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma multiforme, oligodendroglioma, oligodendroglioma, schwannoma, retinoblastoma, and congenital tumors; and cancers of the spinal cord, e.g. neurofibroma, meningioma, glioma, and sarcoma; cancers of the nervous system, including, for example, childhood brain cancers, e.g. astrocytoma, medulloblastoma, glioma, ependymoma, germ cell tumors, e.g. germinoma, and non-germinoma tumors, e.g. teratomas, choriocarcinomas, endodermal sinus tumors (yolk sac tumors), embryonal carcinomas, and mixed tumors.

[0216] 9) Cancer of the uterus, e.g. endometrial cancer (e.g. carcinoma, endometrioid adenocarcinoma, serous carcinoma, clear cell carcinoma, mucinous carcinoma, mixed or undifferentiated carcinoma (including mixed Müllerian tumors), endometrial stromal sarcoma, endometrial squamous cell carcinoma, urothelial carcinoma, endometrial carcinoma with CTNNB1 mutation); Cancer of the cervix, e.g. cervical carcinoma and preneoplastic cervical dysplasia; Cancer of the ovary, e.g. BRCA-mutated ovarian cancer, superficial epithelial and stromal tumors (including ovarian epithelial carcinoma (type 1 (endometrioid, mucinous, clear cell, low-grade serous) or type 2 (poorly differentiated, carcinosarcoma, and high-grade serous))), ovarian carcinoma (serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid tumor, small cell ovarian cancer (hypercalcemic small cell ovarian cancer, pulmonary-type small cell ovarian cancer), unclassified carcinoma, granulosa and theca cell tumor, Sertoli-Leydig cell tumor, dysgerminoma, and malignant teratoma); cancer of the vulva, e.g. squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma, and melanoma; cancer of the vagina, e.g. clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma, and embryonal rhabdomyosarcoma; and cancer of the fallopian tube, e.g. carcinoma, primary fallopian tube carcinoma; Gynecologic cancers, including, for example, primary peritoneal cancer (also known as superficial serous papillary carcinoma, primary peritoneal carcinoma, extraovarian serous carcinoma, primary papillary serous carcinoma, and psammomatous carcinoma).

[0217] 10) Blood cancers, including, for example, acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndromes (refractory cytopenia with monocytic dysplasia (refractory anemia, refractory neutropenia, and refractory thrombocytopenia), refractory anemia with ringed sideroblasts, refractory cytopenia with polycytic dysplasia, refractory anemia with excess blasts I and II, refractory cytopenia of childhood), as well as myeloproliferative neoplasms, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes, myelodysplastic-myeloproliferative disorders, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and Waldenstrom's macroglobulinemia.

[0218] 11) Skin cancers and disorders including, for example, malignant and metastatic melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevi, lipomas, hemangiomas, dermatofibromas, keloids, and scleroderma.

[0219] 12) Adrenal gland cancer, including, for example, neuroblastoma.

[0220] 13) Soft tissue sarcomas (STS), such as fibrosarcoma, malignant fibrous histiocytoma, dermatofibrosarcoma, liposarcoma, rhabdomyosarcoma, leiomyosarcoma, angiosarcoma, Kaposi's sarcoma, lymphangiosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor (also called neurofibrosarcoma, malignant schwannoma, and neurogenic sarcoma), neurofibrosarcoma, extraskeletal chondrosarcoma, extraskeletal osteosarcoma, extraskeletal myxoid chondrosarcoma, extraskeletal mesenchymal, embryonal, and alveolar soft part sarcoma, and infantile hemangiopericytoma.

[0221] More specifically, central nervous system tumors treatable by the compounds, compositions, and methods described herein include:

[0222] 1) Astrocytic tumors, such as diffuse astrocytoma (fibrous, protoplasmic, large round cell, mixed), anaplastic (malignant) astrocytoma, glioblastoma multiforme (giant cell glioblastoma and gliosarcoma), pilocytic astrocytoma (pilocytic myxoid astrocytoma), multiform xanthoastrocytoma, subependymal giant cell astrocytoma, and gliomatosis cerebri.

[0223] 2) Oligodendroglial tumors, such as oligodendroglioma and anaplastic oligodendroglioma.

[0224] 3) Oligoastrocytic tumors, such as oligoastrocytoma and anaplastic oligoastrocytoma.

[0225] 4) Ependymal tumors, such as subependymoma, myxopapillary ependymoma, ependymoma (cellular, papillary, clear cell, elongated cell), and anaplastic (malignant) ependymoma.

[0226] 5) Choroid plexus tumors, such as choroid plexus papilloma, atypical choroid plexus papilloma, and choroid plexus carcinoma.

[0227] 6) Neuronal tumors and mixed neuronal-glial tumors, such as ganglioneuroma, ganglioglioma, dysembryoplastic neuroepithelial tumor (DNET), cerebellar dysplastic ganglioneuroma (Lhermitte-Duclos disease), desmoplastic infantile astrocytoma / ganglioma, central neurocytoma, anaplastic ganglioglioma, extraventricular neurocytoma, cerebellar liponeurocytoma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor of the fourth ventricle, and paraganglioma terminale.

[0228] 7) Pineal tumors, such as pineocytoma, pineoblastoma, pineal papillary tumor, and intermediate pineal parenchymal tumor.

[0229] 8) Embryonal tumors, such as medulloblastoma (medulloblastoma with extensive nodular formation, anaplastic medulloblastoma, desmoplastic, large cell, pigmented, medullomyoblastoma), medulloepithelioma, supratentorial primitive neuroectodermal tumor, and primitive neuroectodermal tumors (PNETs), such as neuroblastoma, ganglioneuroblastoma, ependymoblastoma, and atypical teratoid / rhabdoid tumor.

[0230] 9) Neuroblastic tumors, such as olfactory neuroblastoma, olfactory neuroepithelioma, and adrenal-sympathetic neuroblastoma.

[0231] 10) Glial cell tumors, such as astroblastoma, third ventricular chordomatoid glioma, and angiocentric glioma.

[0232] 11) Tumors of the cranial nerves and paraspinal nerves, such as schwannoma, neurofibroma, perineurioma, and malignant peripheral nerve sheath tumor.

[0233] 12) Meningeal tumors, such as meningeal cell tumors, such as meningiomas (atypical meningiomas and anaplastic meningiomas); mesenchymal tumors, such as lipomas, angiolipomas, brown lipomas, liposarcomas, solitary fibrous tumors, fibrosarcomas, malignant fibrous histiocytomas, leiomyomas, leiomyosarcomas, rhabdomyomas, rhabdomyosarcomas, chondroma, chondrosarcomas, osteomas, osteosarcomas, osteochondroma, hemangiomas, epithelioid hemangioendotheliomas, hemangiopericytomas, anaplastic hemangiopericytomas, hemangiosarcomas, Kaposi's sarcomas, and Ewing's sarcomas; primary melanocytic lesions, such as diffuse melanocytosis, melanocytoma, malignant melanoma, meningeal melanomatosis; and hemangioblastomas.

[0234] 13) Hematopoietic tumors, such as malignant lymphoma, plasmacytoma, and granulocytic sarcoma.

[0235] 14) Germ cell tumors, including germinomas, embryonal carcinomas, yolk sac tumors, choriocarcinomas, teratomas, and mixed germ cell tumors.

[0236] 15) Sellar tumors, such as craniopharyngiomas, granular cell tumors, pituitary cell tumors, and adenohypophyseal spindle cell oncocytomas.

[0237] Cancer can be a solid tumor that may or may not be metastatic.Cancer can also occur as diffuse tissue, similar to leukemia.Therefore, the term "tumor cell" as described herein includes cells that are affected by any one of the above-identified disorders.

[0238] Methods of treating cancer using the compounds or compositions described herein can be combined with existing methods of treating cancer, such as chemotherapy, radiation, or surgery (e.g., oophorectomy). In some embodiments, the compounds or compositions can be administered before, during, or after another anti-cancer agent or treatment.

[0239] Evidence is accumulating for the role of DYRK1A in the pathogenesis of Alzheimer's disease (Future Medicinal Chemistry (2016), 8(6), 681-696 and European Journal of Medicinal Chemistry (2018), 158, 559-592). DYRK1A phosphorylates key substrates involved in Alzheimer's disease and dementia, namely tau, septin 4, amyloid precursor protein (APP), presenilin 1, neprilysin, Munc18-1, α-synuclein, RCAN1, and β-tubulin. By regulating alternative splicing of tau exon 10, DYRK1A preferentially produces the 3R-tau splice isoform (characteristic of DS / AD / tauopathy) over the 4R-tau isoform (Journal of Biological Chemistry (2015), 290, 15219-15237).

[0240] Genome-wide association studies (GWAS) have revealed that DYRK1A is a risk factor for Parkinson's disease (The Lancet Neurology (2019), 18(12), 1091-1102). DYRK1A phosphorylates key factors in Parkinson's disease, such as parkin, septin 4, and α-synuclein. Upregulation of Parkinson's disease-specific microRNAs targets the expression of DYRK1A. Furthermore, there is also evidence that DYRK1A expression is increased in Parkinson's disease and Pick's disease (Neurobiology of Disease (2005), 20(2), 392-400).

[0241] The compounds and compositions provided herein can be used as inhibitors and / or modulators of the enzyme DYRK1A, and thus can be used to treat Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Down's syndrome, FTD-17 with Parkinsonism (FTDP-17), behavioral frontotemporal dementia (bvFTD), frontotemporal dementia (FTD), including FTD in patients with motor neurone disease (MND) (commonly known as amyotrophic lateral sclerosis), also known as FTD-ALS, corticobasal degeneration (CBD) (corticobasal neurodegeneration), and other conditions that may be associated with the development of DYRK1A. It can be used to treat various disorders and diseases associated with tau protein, including, but not limited to, myotonic dystrophy type 1 (DM1) (also called Steinert's disease), myotonic dystrophy type 2 (DM2) (also called proximal myotonic myopathy), Guam complex, argyrophilic grain disease, dementia pugilistica, postencephalitic parkinsonism, dementia with Lewy bodies, Parkinson's disease, Pick's disease, and further diseases with significant neurodegeneration, such as autism, dementia, epilepsy, Huntington's disease, multiple sclerosis; diseases and disorders associated with acquired brain injury, such as chronic traumatic encephalopathy, traumatic brain injury, tumors, and stroke.

[0242] Non-limiting examples of neurological disorders (e.g., neurological conditions or diseases) treatable with the compounds and compositions provided herein include Alzheimer's disease, aphasia, apraxia, arachnoiditis, ataxia telangiectasia, attention deficit hyperactivity disorder, auditory processing disorder, autism, alcoholism, Bell's palsy, bipolar disorder, brachial plexus injury, Canavan disease, carpal tunnel syndrome, causalgia, central pain syndrome, central pontine myelinolysis, centronuclear myopathy, head disorder, cerebral aneurysm, cerebral arteriosclerosis, cerebral atrophy, cerebral gigantism, cerebral palsy, cerebral vasculitis, cervical spinal stenosis, Charcot-Marie-Tu Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), chronic pain, Coffin-Lowry syndrome, complex regional pain syndrome, compressive neuropathy, congenital bilateral facial palsy, corticobasal degeneration, cranial arteritis, craniosynostosis, Creutzfeldt-Jakob disease, cumulative trauma disorder, Cushing's syndrome, cytomegalic inclusion disease (CIBD), Dandy-Walker syndrome, Dawson's disease, Domorsia syndrome, Dejerine-Klumpke palsy, Dejerine-Sottas disease, delayed sleep phase syndrome, dementia, dermatomyositis, development Coordination disorder, diabetic neuropathy, diffuse sclerosis, Dravet syndrome, autonomic neuropathy, dyscalculia, dysgraphia, dyslexia, dystonia, empty sella syndrome, encephalitis, cerebral herniation, trigeminal nerve region angiomatosis, encopresis, epilepsy, Erb's palsy, erythromelalgia, essential tremor, Fabry disease, Fahr's syndrome, familial spastic paralysis, febrile seizures, Fisher syndrome, Friedreich's ataxia, fibromyalgia, Foville syndrome, Gaucher disease, Gerstmann syndrome, giant cell arteritis, giant cell inclusion disease, globoid cell leukodystrophy, ectopic gray matter, Guillain-Barr syndrome ·Barre syndrome, HTLV-1-associated myelopathy, Hallervorden-Spatz disease, hemifacial spasm, hereditary spastic paraplegia, hereditary polyneuropathic ataxia, otitis zoster, herpes zoster, Hirayama syndrome, holoprosencephaly, Huntington's disease, hydranencephaly, hydrocephalus, hypercortisolism, hypoxia, immune-mediated encephalomyelitis, inclusion body myositis, incontinentia pigmenti, infantile phytanic acid storage disease, infantile Refsum disease, infantile spasms, inflammatory myopathy, intracranial cysts, increased intracranial pressure, Joubert syndrome, Karak syndrome, Kearns-Sayre syndrome, Kennedy disease, Kinsbone syndrome, Klippel-Feil syndrome, Krabbe disease,Kugelberg-Welander disease, kuru disease, Lafora disease, Lambert-Eaton myasthenic syndrome, Landau-Kleffner syndrome, lateral medullary syndrome (Wallenberg syndrome), Leigh disease, Lennox-Gastaut syndrome, Lesch-Nyhan syndrome, leukodystrophy, dementia with Lewy bodies, gliosis, locked-in syndrome, Lou Gehrig's disease, lumbar disc disease, lumbar spinal stenosis, Lyme disease, Machado-Joseph disease (spinocerebellar ataxia type 3), macrocephaly, macropsia, megalencephaly, Melkersson-Rosenthal syndrome, Ménière's disease, meningitis, Menkes disease, metachromatic white matter Dystrophy, microcephaly, micropsia, Miller Fisher syndrome, phonophobia, mitochondrial myopathy, Moebius syndrome, juvenile unilateral upper limb muscular atrophy, motor neuron disease, motor ability disorder, Moyamoya disease, mucopolysaccharidosis, multiple infarct dementia, multifocal motor neuropathy, multiple sclerosis, multiple system atrophy, muscular dystrophy, myalgic encephalomyelitis, myasthenia gravis, myelin destructive diffuse sclerosis, infantile myoclonic encephalopathy, myoclonus, myopathy, myotubular myopathy, congenital myotonia, narcolepsy, neurofibromatosis, neuroleptic malignant syndrome, lupus erythematosus, neuromuscular Ankylosis, Neuronal ceroid lipofuscinosis, Niemann-Pick disease, O'Sullivan-McLeod syndrome, Occipital neuralgia, Spina bifida occulta, Ohtahara syndrome, Olivopontocerebellar atrophy, Opsoclonus-myoclonus syndrome, Optic neuritis, Orthostatic hypotension, Recurrent vision, Paresthesias, Parkinson's disease, Congenital paramyotonia, Paraneoplastic disease, Paroxysmal seizures, Parry-Romberg syndrome, Pelizaeus-Merzbach disease, Periodic paralysis, Peripheral neuropathy, Photophotic sneeze reflex, Phytanic acid storage disease, Pick's disease, Polymicrogyria (PMG), Polymyositis, Porencephaly, Post-polio syndrome, Zoster syndrome Postherpetic neuralgia (PHN), postural hypotension, Prader-Willi syndrome, primary lateral sclerosis, prion disease, progressive facial hemiatrophy, progressive multifocal leukoencephalopathy, progressive supranuclear palsy, pseudotumor cerebri, Ramsay Hunt syndrome type I, Ramsay Hunt syndrome type II, Ramsay Hunt syndrome type III, Rasmussen encephalitis, reflex neurovascular dystrophy, Refsum disease, restless legs syndrome, retrovirus-associated myelopathy, Rett syndrome, Reye syndrome, rhythmic movement disorder, Romberg syndrome, chorea, Sandhoff disease, schizophrenia, Schilder's disease, schizencephaly, sensory integration dysfunction,Septo-optic dysplasia, Shy-Drager syndrome, Sjögren's syndrome, snatiation, Sotos syndrome, spasticity, spina bifida, spinal cord tumor, spinal muscular atrophy, spinocerebellar ataxia, Steele-Richardson-Olszewski syndrome, stiff-person syndrome, stroke, Sturge-Weber syndrome, subacute sclerosing panencephalitis, subcortical arteriosclerotic encephalopathy, superficial siderosis, Sydenham chorea, syncope, synesthesia, syringomyelia, tarsal tunnel syndrome, tardive dyskinesia, tardive dysphrenia, Tarlov cyst, Tay-Sachs disease, temporal arteritis, tetanus, tethered spinal cord syndrome, Thomsen's disease, thoracic outlet syndrome, trigeminal neuralgia (tic douloureux, Todd's palsy, Tourette's syndrome, toxic encephalopathy, transient ischemic attacks, transmissible spongiform encephalopathy, transverse myelitis, tremors, trigeminal neuralgia, tropical spastic paraparesis, trypanosomiasis, tuberous sclerosis, ubisiosis, von Hippel-Lindau disease (VHL), Viliuisk encephalomyelitis (VE), Wallenberg syndrome, Werdnig-Hoffmann disease, West syndrome, Williams syndrome, Wilson's disease, and Zellweger syndrome.

[0243] The compounds and compositions may also be useful in inhibiting invasive carcinogenesis, tumor angiogenesis, and metastasis.

[0244] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a compound of formula (I), or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable excipient.

[0245] In some embodiments, the disorder or disease is cancer.

[0246] In some embodiments, the disorder or disease is metastatic melanoma.

[0247] In some embodiments, the disorder or disease is tendon regeneration.

[0248] In some embodiments, the disorder or disease is diabetes.

[0249] In some embodiments, the disorder or disease is degenerative disc disease.

[0250] In some embodiments, the disorder or disease is osteoarthritis.

[0251] In some embodiments, the disorder or disease is a viral infection.

[0252] In some embodiments, the disorder or disease is a neurological disorder.

[0253] In some embodiments, the disorder or disease is Alzheimer's disease.

[0254] In some embodiments, the disorder or disease is osteoarthritis.

[0255] In some embodiments, the patient is a human.

[0256] In some embodiments, the cancer is selected from hepatocellular carcinoma, colon cancer, breast cancer, pancreatic cancer, chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia, chronic lymphocytic leukemia (CLL), acute myelogenous leukemia, acute lymphocytic leukemia, Hodgkin's lymphoma, lymphoma, sarcoma, and ovarian cancer.

[0257] In some embodiments, the cancer is selected from non-small cell lung cancer, small cell lung cancer, multiple myeloma, nasopharyngeal cancer, neuroblastoma, osteosarcoma, penile cancer, pituitary tumor, prostate cancer, retinoblastoma, synovial sarcoma, rhabdomyosarcoma, salivary gland cancer, basal and squamous cell skin cancer, skin cancer (melanoma), small intestine cancer, gastric cancer, testicular cancer, thymic cancer, thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer, laryngeal or hypopharyngeal cancer, renal cancer, Kaposi's sarcoma, gestational trophoblastic disease, gastrointestinal stromal tumor, gastrointestinal carcinoid tumor, gallbladder cancer, eye cancer (melanoma and lymphoma), Ewing's tumor, esophageal cancer, endometrial cancer, colorectal cancer, cervical cancer, brain or spinal tumor, bone metastasis, bone cancer, bladder cancer, bile duct cancer, anal cancer, and adrenal cortical carcinoma.

[0258] In some embodiments, the cancer is hepatocellular carcinoma; in some embodiments, the cancer is colon cancer; in some embodiments, the cancer is colorectal cancer; in some embodiments, the cancer is breast cancer; in some embodiments, the cancer is pancreatic cancer; in some embodiments, the cancer is chronic myelogenous leukemia (CML); in some embodiments, the cancer is chronic myelomonocytic leukemia; in some embodiments, the cancer is chronic lymphocytic leukemia (CLL); in some embodiments, the cancer is acute myelogenous leukemia; in some embodiments, the cancer is acute lymphocytic leukemia; in some embodiments, the cancer is Hodgkin's lymphoma; in some embodiments, the cancer is lymphoma; in some embodiments, the cancer is sarcoma; in some embodiments, the cancer is ovarian cancer; in some embodiments, the cancer is non-small cell lung cancer; in some embodiments, the cancer is small cell lung cancer; in some embodiments, the cancer is multiple myeloma; in some embodiments, the cancer is nasopharyngeal carcinoma; in some embodiments, the cancer is neuroblastoma; In some embodiments, the cancer is osteosarcoma; in some embodiments, the cancer is penile cancer; in some embodiments, the cancer is a pituitary tumor; in some embodiments, the cancer is prostate cancer; in some embodiments, the cancer is retinoblastoma; in some embodiments, the cancer is rhabdomyosarcoma; in some embodiments, the cancer is salivary gland cancer; in some embodiments, the cancer is basal cell-squamous cell skin cancer; in some embodiments, the cancer is skin cancer (melanoma); in some embodiments, the cancer is small intestine cancer; in some embodiments, the cancer is gastric cancer; in some embodiments, the cancer is testicular cancer; in some embodiments, the cancer is thymic cancer; in some embodiments, the cancer is thyroid cancer; in some embodiments, the cancer is uterine sarcoma; in some embodiments, the cancer is vaginal cancer; in some embodiments, the cancer is vulvar cancer; in some embodiments, the cancer is Wilms' tumor; in some embodiments, the cancer is laryngeal or hypopharyngeal cancer; in some embodiments, the cancer is renal cancer; in some embodiments, the cancer is Kaposi's sarcoma; In some embodiments, the cancer is gestational trophoblastic disease;In some embodiments, the cancer is a gastrointestinal stromal tumor; in some embodiments, the cancer is a gastrointestinal carcinoid tumor; in some embodiments, the cancer is a gallbladder cancer; in some embodiments, the cancer is an eye cancer (melanoma and lymphoma); in some embodiments, the cancer is a Ewing's tumor; in some embodiments, the cancer is an esophageal cancer; in some embodiments, the cancer is an endometrial cancer; in some embodiments, the cancer is a colorectal cancer; in some embodiments, the cancer is a cervical cancer; in some embodiments, the cancer is a brain or spinal tumor; in some embodiments, the cancer is a bone metastasis; in some embodiments, the cancer is a bone cancer; in some embodiments, the cancer is a bladder cancer; in some embodiments, the cancer is a bile duct cancer; in some embodiments, the cancer is anal cancer; in some embodiments, the cancer is an adrenocortical carcinoma;

[0259] In some embodiments, the disorder or disease is a neurological condition, neurological disorder, or neurological disease, and the neurological disease is selected from Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, amyotrophic lateral sclerosis (ALS), inclusion body myositis, autism, and degenerative muscle disorders.

[0260] In some embodiments, the disorder or disease is selected from the group consisting of Alzheimer's disease, amyotrophic lateral sclerosis, Down's syndrome, frontotemporal dementia with parkinsonism-17 (FTDP-17), dementia with Lewy bodies, Parkinson's disease, Pick's disease, and additional diseases with significant neurodegeneration, such as autism, dementia, epilepsy, Huntington's disease, multiple sclerosis; diseases and disorders associated with acquired brain injury, such as chronic traumatic encephalopathy, traumatic brain injury, tumors, and stroke.

[0261] In some embodiments, the compounds of Formula (I) inhibit DYRK1A.

[0262] In some embodiments, the method is for treating a disease or disorder mediated by kinase activity in a patient, the method comprising administering to the patient a therapeutically effective amount of a compound(s) of Formula (I), or a pharma- ceutically acceptable salt thereof.

[0263] In some embodiments, the disease or disorder involves tumor growth, cell proliferation, or angiogenesis.

[0264] In some embodiments, the method inhibits activity of a protein kinase receptor, the method comprising contacting the receptor with an effective amount of a compound or compounds of Formula (I), or a pharma- ceutically acceptable salt thereof.

[0265] In some embodiments, the method is for treating a disease or disorder associated with abnormal cell proliferation in a patient, the method comprising administering to the patient a therapeutically effective amount of a compound(s) of formula (I), or a pharmaceutically acceptable salt thereof.

[0266] In some embodiments, the methods prevent or reduce abnormal cell proliferation in a patient, the methods comprising administering to the patient a therapeutically effective amount of a compound(s) of formula (I), or a pharmaceutically acceptable salt thereof.

[0267] In some embodiments, the method is for treating a disease or disorder associated with abnormal cell proliferation in a patient, the method comprising administering to the patient a pharmaceutical composition comprising one or more compounds of claim 1 in combination with a pharma- ceutically acceptable carrier and one or more other agents.

[0268] Evaluation of Biological Activity The biological activity of the compounds described herein can be tested using any suitable assay known to those skilled in the art. For example, the activity of the compounds can be tested using one or more of the test methods outlined below.

[0269] For example, an in vitro assay for the biological activity of DYRK1A, for example, the regulation of phosphorylation of microtubule-associated protein tau (MAPT / tau) in a neuronal cell line, such as the human SH-SY5Y neuroblastoma cell line, can be used. The assay for DYRK1A-regulated phosphorylation level can include monitoring the level of basal pSer396 tau, which can be measured by serial dilution of a candidate inhibitor composition, for example, using a top concentration of 10 micromolar, and detected by ELISA or Western blotting. An exemplary assay for DYRK-1A-regulated phosphorylation uses SH-SY5Y cells, which are cultured in a 96-well plate format for a sufficient period of time to stabilize the phosphorylation of microtubules and tau, usually at least 2 days, and then treated overnight with 1 / 3 serial dilutions of compounds and lysed. The cell lysates are separated by SDS PAGE, transferred to nitrocellulose, and probed with an antibody specific for pSer396 tau. Chemiluminescent signals of HRP-conjugated antibodies used in Western blotting are detected using a Carestream Image Station, and blot densitometry of pSer396 and β-actin is analyzed using ImageJ (NIH).

[0270] In a further example, the activity of candidate compounds can be measured by phosphorylated tau (Thr212) AlphaLISA by adding the above-mentioned lysate onto whole tau coated plates and detecting with a specific pThr212 tau antibody. Colorimetric detection of the AlphaLISA signal is performed by an EnVision multilabel plate reader (Perkin Elmer).

[0271] The following examples are included to further illustrate the present disclosure. Of course, the examples should not be construed as specifically limiting the present disclosure. Variations of these examples within the scope of the claims are within the skill of one of ordinary skill in the art and are considered to be within the scope of the present disclosure as described and claimed herein. The reader will recognize that a person skilled in the art, armed with this disclosure and the skills in the art, can prepare and use the present disclosure without the exhaustive examples. EXAMPLES

[0272] Preparation of Compounds The compounds used in preparing the compounds of the present disclosure are known, made by known methods, or are commercially available.It will be clear to those skilled in the art that the methods for preparing the precursors and functional groups related to the compounds claimed herein are generally described in the literature.Given the literature and this disclosure, those skilled in the art are fully prepared to prepare any compound.

[0273] It will be recognized that one of ordinary skill in the art of organic chemistry can readily perform these manipulations without further instruction, i.e., it is well within the scope and practice of the art to perform these manipulations. These include reduction of carbonyl compounds to the corresponding alcohols, oxidation, acylation, aromatic substitutions, both electrophilic and nucleophilic, etherification, esterification, and saponification. These manipulations are described in March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure 7. th Ed., John Wiley & Sons (2013), Carey and Sundberg, Advanced Organic Chemistry 5 th Ed., Springer (2007), Comprehensive Organic Transformations: A Guide to Functional Group Transformations, 2 ndEd., John Wiley & Sons (1999), which is incorporated herein by reference in its entirety.

[0274] Those skilled in the art will easily recognize that certain reactions are best performed when other functional groups in the molecule are shielded or protected to avoid any undesired side reactions and / or increase the yield of the reaction. Often, those skilled in the art will utilize protective groups to achieve this increased yield or to avoid undesired reactions. These reactions can be found in the literature and are also well within the scope of those skilled in the art. Examples of many of these manipulations can be found, for example, in Protective Groups in Organic Synthesis, 5th Ed., John Wiley & Sons (2014) by P. Wuts Greene, which is incorporated herein by reference in its entirety.

[0275] The trademarks used herein are only examples and are intended to indicate exemplary materials used at the time of this disclosure. One of ordinary skill in the art will recognize that variations in lots, manufacturing runs, etc. are to be expected. Thus, the examples and the trademarks used in the examples are non-limiting and are not intended to be limiting, but merely illustrative of how one of ordinary skill in the art may select to implement one or more aspects of the present disclosure.

[0276] ( 1 H) Nuclear magnetic resonance (NMR) spectra were measured using a Bruker NMR spectrometer (Avance™ DRX300, 1 H is 300MHz, or Avance TM DRX500, 1 H is 500MHz) or a Varian NMR spectrometer (Mercury 400BB, 1H was measured in the indicated solvents at 400 MHz. Peak positions are in parts per million (ppm) downfield from tetramethylsilane. Peak multiplicities are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; ABq, AB quartet; quin, quintet; sex, sextet; sep, septet; non, nonet; dd, doublet of doublet; ddd, doublet of doublet doublet; d / ABq, AB quartet doublet; dt, triplet doublet; td, doublet of doublet; dq, quartet doublet; m, multiplet.

[0277] The following abbreviations have the indicated meanings: Ac2O = acetic anhydride Brine = saturated aqueous sodium chloride solution t BuOK = potassium tert-butoxide CDCl3 = deuterated chloroform m-CPBA = meta-chloroperbenzoic acid Cs2CO3 = Cesium carbonate DCE = dichloroethane DCM = dichloromethane DIPEA = N,N-diisopropylethylamine DME = dimethoxyethane, or glyme, or monoglyme DMF = N,N-dimethylformamide DMPU = N,N'-dimethylpropylene urea DMSO-d6 = deuterated dimethyl sulfoxide ESIMS = Electrospray Mass Spectrometry EtOAc = ethyl acetate HATU = 1-bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate HCl = Hydrochloric Acid HOAc = acetic acid ISCO = Teledyne ISCO, Inc. brand CombiFlash® Rf 200 KOAc = Potassium Acetate LC / MS = liquid chromatography mass spectrometry MeCN = acetonitrile MeOH = methanol MgSO4 = Magnesium sulfate Monoglyme = 1,2-dimethoxyethane MsCl = mesyl chloride or methanesulfonyl chloride MW = microwave radiation NaHCO3 = sodium bicarbonate Na(OAc)3BH = sodium triacetoxyborohydride Na2SO4 = Sodium sulfate NMR = nuclear magnetic resonance ON = All night PCy3 = tricyclohexylphosphine Pd / C = palladium on carbon Pd2(dba)3 = tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)Cl2 = 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride Pd(OH)2 / C = palladium hydroxide on carbon prep-TLC = preparative thin-layer chromatography rt = room temperature SM = starting material T3P = phosphonic anhydride propane TEA = triethylamine TFA = trifluoroacetic acid THF = Tetrahydrofuran TLC = thin layer chromatography

[0278] The following exemplary schemes are provided as a guide for the reader and collectively represent exemplary methods for making the compounds described herein.In addition, other methods for preparing the compounds of the present disclosure will be readily apparent to those skilled in the art in light of the following reaction schemes and examples.Given the literature and this disclosure, those skilled in the art are fully prepared to prepare these compounds by those methods.The numbering of the compounds used in the synthetic schemes shown below is intended only with respect to those specific schemes and should not be interpreted or confused with the same numbering in other sections of this application.Unless otherwise indicated, all variables are as defined above.

[0279] General Procedures Compounds of formula I of the present disclosure can be prepared as shown in Scheme 1. TIFF2024539620000110.tif81157

[0280] Scheme 1 describes a method for the preparation of pyrrolo[2,1-f][1,2,4]triazine derivatives (VI) by first coupling chlorides (I) with various amines (II) to produce bromopyrrolo[2,1-f][1,2,4]triazines III. Various bromides (IV) are reacted with bis(pinacolato)diboron to form various boronic acid pinacol esters, followed by Suzuki coupling with bromides (IV) to produce the final pyrrolo[2,1-f][1,2,4]triazines (VI). Alternatively, various commercially available boronic acid pinacol esters (V) can be directly coupled with bromides (III) to produce the final pyrrolo[2,1-f][1,2,4]triazines (VI).

[0281] Compounds of formula I of the present disclosure can also be prepared as shown in Scheme 2. TIFF2024539620000111.tif89159

[0282] In scheme 2, a method is described for the preparation of pyrrolo[2,1-f][1,2,4]triazine derivatives (VI) by oxidation of sulfide VII to sulfone VIII. Sulfone VIII can then be coupled with various amines (II) to generate bromopyrrolo[2,1-f][1,2,4]triazine III, followed by Suzuki coupling with various boronic acids (IX) to generate the final pyrrolo[2,1-f][1,2,4]triazine (VI). Alternatively, various boronic acids (IX) can be coupled with sulfone VIII, followed by coupling with various amines (II) to generate the final pyrrolo[2,1-f][1,2,4]triazine (VI).

[0283] Compound Examples The preparation of the intermediate 6-bromo-1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridine (XV) is depicted below in Scheme 3. TIFF2024539620000112.tif88146

[0284] Step 1 A mixture of 2,2-difluoroethan-1-amine (XII) (410 mg, 5.02 mmol), 5-bromo-3-fluoro-2-nitropyridine (XI) (commercially available from Ark Pharma Scientific Limited) (1.0 g, 4.53 mmol), and K2CO3 (1.38 g, 9.95 mmol) in MeCN (20 mL) was stirred at room temperature for 16 h. The reaction was filtered and concentrated under high vacuum. The residue was taken up in water and stirred for 1 h, and the solid was collected by filtration and dried under reduced pressure to give 5-bromo-N-(2,2-difluoroethyl)-2-nitropyridin-3-amine (XIII) (1.066 g, 3.780 mmol, 83.5% yield) as a yellow solid which was used in the next step without purification. ESIMS found m / z 282.0 for C7H6BrF2N3O2 ( 79 BrM+H).

[0285] Step 2 A mixture of 5-bromo-N-(2,2-difluoroethyl)-2-nitropyridin-3-amine (XIII) (1.32 g, 4.69 mmol), Fe (3.07 g, 46.95 mmol), and NH4Cl (3.77 g, 70.48 mmol) was taken up in a mixture of EtOH (18 mL) and water (6 mL) and the mixture was heated to 70° C. for 4 h. The reaction mixture was cooled and filtered through Celite®. The filtrate was taken up in EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give 5-bromo-N 3 -(2,2-Difluoroethyl)pyridine-2,3-diamine (XIV) (630 mg, 2.499 mmol, 53.2% yield) was obtained as a grey solid, which was used in the next reaction without further purification. ESIMS found m / z 252.0 for C7H8BrF2N3 ( 79 BrM+H).

[0286] Step 3 5-Bromo-N 3 A solution of -(2,2-difluoroethyl)pyridine-2,3-diamine (XIV) (630 mg, 2.5 mmol) and acetic anhydride (0.28 mL, 2.97 mmol) in HOAc (15 mL) was heated to 120 °C for 16 h. The reaction mixture was concentrated and the residue was partitioned between EtOAc / 1N NaOH, the organic layer was separated and washed with water and brine. The organic layer was dried over anhydrous Na2SO4 and the solvent was concentrated under high vacuum. The residue was triturated with diethyl ether, sonicated, the solid was collected by filtration and dried under high vacuum to give 6-bromo-1-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (XV) (325 mg, 1.177 mmol, 47.1% yield) as a grey solid which was used in the next step without purification. ESIMS found m / z 276.0 for C9H8BrF2N3 ( 79 BrM+H).

[0287] The following intermediates were prepared according to the procedures described in Scheme 3 above.

[0288] TIFF2024539620000113.tif341286-Bromo-1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridine (XVI): Grey solid (1.57 g, 6.178 mmol, 68.3% yield). ESIMS C 11 H 10 Found m / z for BrF2N3: 302.1 (M+H).

[0289] TIFF2024539620000114.tif361286-Bromo-1-(2,2-difluoroethyl)-2-methyl-1H-benzo[d]imidazole (XVII): beige solid (970 mg, 3.526 mmol, 79.0% yield). ESIMS C 10 Measured m / z for H9BrF2N2: 275.0 (M+H).

[0290] The preparation of the intermediate 6-bromo-1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridine (XXII) is depicted below in Scheme 4. TIFF2024539620000115.tif89128

[0291] Step 1 A mixture of 2-aminopropane (XIX) (0.86 mL, 9.96 mmol), 5-bromo-3-fluoro-2-nitropyridine (XVIII) (2 g, 9.05 mmol), and K2CO3 (2.5 g, 18.1 mmol) in MeCN (40 mL) was stirred at room temperature for 16 h. The reaction mixture was added to water (200 mL), stirred for 1 h, and the resulting solid was collected by filtration and dried under high vacuum to give 5-bromo-N-isopropyl-2-nitropyridin-3-amine (XX) (2.36 g, 9.074 mmol, 100.3% yield) as a yellow solid, which was used in the next step without purification. ESIMS C8H 10 Measured value for BrN3O2: m / z 260.0 (M+H).

[0292] Step 2 A mixture of 5-bromo-N-isopropyl-2-nitropyridin-3-amine (XX) (2.35 g, 9.04 mmol), Fe (5.91 g, 90.35 mmol), and NH4Cl (7.25 g, 135.53 mmol) was taken up in a mixture of EtOH (30 mL) and water (10 mL) and the mixture was heated to 70° C. for 2 h. The reaction mixture was cooled and filtered through Celite®, and the filtrate was taken up in EtOAc, washed with water and then with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give 5-bromo-N 3 -Isopropylpyridine-2,3-diamine (XXI) (2.2 g, 9.561 mmol, 105.8% yield) was obtained as a dark brown solid, which was used in the next step without purification. ESIMS C8H 12 Found m / z for BrN3: 230.05 (M+H).

[0293] Step 3 5-Bromo-N 3 A solution of 1-isopropylpyridine-2,3-diamine (XXI) (2.08 g, 9.04 mmol) and Ac2O (1.05 mL, 10.84 mmol) in HOAc (20 mL) was heated to 120 °C for 16 h. The reaction mixture was concentrated, the residue was partitioned between EtOAc / 1N NaOH, the organic layer was separated and washed with water and brine. The organic layer was dried over anhydrous Na2SO4, the solvent was concentrated and dried under high vacuum to give 6-bromo-1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridine (XXII) (1.57 g, 6.178 mmol, 68.3% yield) as a dark brown solid, which was used in the next step without purification. ESIMS C 10 H 12 Measured value for BrN3: m / z 254.0 (M+H).

[0294] The following intermediates were prepared according to the procedures described in Scheme 4 above.

[0295] TIFF2024539620000116.tif341286-Bromo-2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridine (XXIII): Grey solid (722 mg, 2.438 mmol, 66.3% yield). ESIMS C 12 H 14 Found m / z for BrNO: 296.0 (M+H).

[0296] TIFF2024539620000117.tif381286-Bromo-1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridine (XXIV): Grey solid (325 mg, 1.177 mmol, 47.1% yield). ESIMS found m / z 276.0 (M+H) for C9H8BrF2N3.

[0297] The preparation of intermediate (R)-2-((6-bromo-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)methyl)-5-(1-fluoroethyl)-1,3,4-oxadiazole (XXXI) is depicted below in Scheme 5. TIFF2024539620000118.tif118130

[0298] Step 1 tA mixture of BuOK (2.1 g, 18.71 mmol) and 6-bromo-2-methyl-3H-imidazo[4,5-b]pyridine (XXV) (4 g, 18.86 mmol) in THF (40 mL) was stirred at 50° C. for 20 min. To the mixture was added methyl bromoacetate (XXVI) (1.98 mL, 20.92 mmol). The mixture was stirred at 50° C. for 1 h. The reaction was quenched with HOAc / water (1 / 10, 10 mL) at 0° C., and the mixture was diluted with EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL). The mixture was concentrated, the precipitate was collected by filtration, and the resulting solid was washed with water and a small amount of EtOAc to give a light brown compound with two products. The aqueous phase was extracted with CHCl3 (3*50 mL), combined with the solid and purified by silica gel column chromatography (0→40% 1.7N NH3MeOH in) to produce two sets of fractions with the correct molecular weight by LC / MS. The less polar fraction was isolated as the by-product methyl 2-(6-bromo-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)acetate (XXVII) (1.48 g, 5.209 mmol, 27.6% yield). The more polar fraction was isolated as the desired product, methyl 2-(6-bromo-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)acetate (XXVIII) (2.43 g, 8.55 mmol, 45.3% yield) as an off-white solid. TIFF2024539620000120.tif18153

[0299] Step 2 A suspension of methyl 2-(6-bromo-2-methylimidazo[4,5-b]pyridin-1-yl)acetate (XXVIII) (2.35 g, 8.27 mmol) in EtOH (26 mL) / water (1.3 mL) was stirred at 70° C. for 10 min (clear yellow solution). Hydrazine hydrate (3.6 mL, 73.86 mmol) was added to the mixture and the mixture was stirred at 70° C. for 4 h (off-white precipitate formed). The reaction was cooled to room temperature and concentrated. The precipitate was collected by filtration and washed with EtOH to give 2-(6-bromo-2-methylimidazo[4,5-b]pyridin-1-yl)acetohydrazide (XXIX) (1.94 g, 6.828 mmol, 82.6% yield) as an off-white solid. TIFF2024539620000121.tif18153

[0300] Step 3 (2R)-2-Fluoropropanoic acid (XXX) (0.16 g, 1.76 mmol), 2-(6-bromo-2-methylimidazo[4,5-b]pyridin-1-yl)acetohydrazide (XXIX) (0.5 g, 1.76 mmol), T3P EtOAc solution (1.2 mL, 2.06 mmol), and DIPEA (0.89 mL, 5.11 mmol) were added to butyl acetate (11 mL) in a microwave vial at room temperature. The vial was sealed and the mixture was stirred at 50 °C for 30 min, a second portion of T3P EtOAc solution (1.2 mL, 2.06 mmol) was added to the mixture, and the resulting mixture was heated to 135 °C for 3 h. The reaction was still not complete. A third portion of T3P EtOAc solution (0.58 mL, 1 mmol) was added, and the mixture was stirred at 135 °C for another 3 h. After the mixture was cooled, saturated aqueous NaHCO3 (30 mL) was added to the mixture. The liquid layer was extracted with EtOAc (75 mL*3), and the organic layer was washed with water and saturated brine, and dried over Na2SO4. The organic layer was purified by silica gel column chromatography (0→5% MeOH / CHCl3) to give (R)-2-((6-bromo-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)methyl)-5-(1-fluoroethyl)-1,3,4-oxadiazole (XXXI) (430 mg, 1.264 mmol, 71.8% yield) as an off-white solid. TIFF2024539620000122.tif18153

[0301] The preparation of the intermediate 5-chloro-3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridine (XXXIII) is depicted below in Scheme 6. TIFF2024539620000123.tif42128

[0302] Step 1 A mixture of 5-chloro-2-methyl-3H-imidazo[4,5-b]pyridine (XXXII) (commercially available from eNovation Chemicals, LLC) (500 mg, 2.98 mmol), iodoethane (560 mg, 3.58 mmol), and K2CO3 (830 mg, 5.97 mmol) in DMF (10 mL) was heated to 70 °C overnight. The reaction mixture was cooled, the solvent was concentrated, the residue was partitioned between EtOAc / water, the organic layer was separated, washed with brine, dried over anhydrous MgSO4, the solvent was concentrated under reduced pressure, and dried to give 5-chloro-3-ethyl-2-methylimidazo[4,5-b]pyridine (XXXIII) (466 mg, 2.382 mmol, 79.8% yield) as a dark brown solid, which was used in the next step without purification. ESIMS C9H 10 Found m / z for ClN3: 196.05 (M+H).

[0303] The following intermediates were prepared according to the procedures described in Scheme 6 above.

[0304] TIFF2024539620000124.tif381285-Chloro-3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridine (XXXIV): beige solid (830 mg, 3.583 mmol, 60.1% yield). ESIMS found m / z 232.0 (M+H) for C9H8ClF2N3.

[0305] TIFF2024539620000125.tif371285-Chloro-3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridine (XXXV): beige solid (220 mg, 1.030 mmol, 57.5% yield). ESIMS found for C9H9ClFN3 m / z 214.05 (M+H).

[0306] TIFF2024539620000126.tif371285-Chloro-3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridine (XXXVI): beige solid (195 mg, 0.864 mmol, 48.3% yield). ESIMS C 10 H 12 Found m / z for ClNO: 226.1 (M+H).

[0307] TIFF2024539620000127.tif421281-(5-Chloro-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-2-methylpropan-2-ol (XXXVII): white solid (229.9 mg, 0.959 mmol, 39.7% yield). TIFF2024539620000128.tif18153

[0308] TIFF2024539620000129.tif381285-Chloro-3-isobutyl-2-methyl-3H-imidazo[4,5-b]pyridine (XXXVIII): white solid (206.8 mg, 0.925 mmol, 38.7% yield). TIFF2024539620000130.tif25153

[0309] TIFF2024539620000131.tif361285-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-3H-imidazo[4,5-b]pyridine (XXXIX): beige solid (372 mg, 1.490 mmol, 50.0% yield). ESIMS found m / z 250.0 (M+H) for C9H7ClF3N3.

[0310] TIFF2024539620000132.tif421285-Chloro-2-methyl-3-(oxetan-3-ylmethyl)-3H-imidazo[4,5-b]pyridine (XL): light brown solid (289.7 mg, 1.219 mmol, 40.4% yield). TIFF2024539620000133.tif25153

[0311] TIFF2024539620000134.tif43128 tert-Butyl 3-((5-chloro-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl)azetidine-1-carboxylate (XLI): Off-white amorphous solid (532.6 mg, 1.581 mmol, 52.1% yield). ESIMS C 16 H 21 Found m / z for ClN4O2: 337.1 (M+H).

[0312] TIFF2024539620000135.tif391282-(5-Chloro-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-N,N-dimethylacetamide (XLII): Off-white solid (474.4 mg, 1.877 mmol, 62.6% yield). ESIMS C 11 H 13 Found m / z for ClNO: 253.1 (M+H).

[0313] TIFF2024539620000136.tif371283-(5-Chloro-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-2,2-dimethylpropanenitrile (XLIII): Off-white amorphous solid (59.1 mg, 0.238 mmol, 7.9% yield). ESIMS C 12 H 13 Found m / z for ClN4: 249.1 (M+H).

[0314] TIFF2024539620000137.tif38128Inseparable mixture of 5-bromo-1-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyrazine (XLIV) and 5-bromo-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyrazine (XLV) as a brown solid (556 mg, 2.007 mmol, 40.7% yield). ESIMS found m / z 277.0 (M+H) for C8H7BrF2N4. Used as mixture for synthesis of compounds 1970 and 1971. Final compounds were separated by chiral supercritical fluid chromatography (SFC).

[0315] The preparation of intermediate 6-bromo-1-(2,2-difluoroethyl)-1H-benzo[d][1,2,3]triazole (XLIX) is shown below in Scheme 7. TIFF2024539620000138.tif45148

[0316] Step 1 A solution of 4-bromo-2-fluoro-1-nitrobenzene (XLVI) (20.0 g, 98.03 mmol) in THF (500.0 mL) was cooled to 0° C. Cs2CO3 (63.9 g, 196.06 mmol) was added and 2,2-difluoroethan-1-amine (XLVII) (36.6 g, 183.81 mmol) was added at 0° C. The reaction was warmed to 40° C. for 16 h. The reaction mixture was extracted with EtOAc (500 Lx3). The combined organic layers were washed with brine (500 mLx3). The combined organic layers were dried over Na2SO4, filtered and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (10→20% EtOAc / petroleum ether) to give 5-bromo-N-(2,2-difluoroethyl)-2-nitroaniline (XLVIII) (23 g, 81.83 mmol, 83.5% yield) as a yellow solid. TIFF2024539620000139.tif25153

[0317] Step 2 To a solution of 5-bromo-N-(2,2-difluoroethyl)-2-nitroaniline (XLVIII) (12.0 g, 42.86 mmol) in HOAc / HCl (500 / 50 mL) was added Fe (30.0 g, 428.62 mmol). The reaction mixture was stirred at 50° C. for 30 min, then cooled to room temperature and filtered. Then, a solution of NaNO2 (3.0 g, 53.58 mmol) in water (20 mL) was added dropwise to the above acidic solution at 0° C. The reaction solution was stirred at 0° C. for 1 h. The reaction mixture was concentrated to dryness and the reaction mixture was poured into EtOAc (300 mL) and H2O (300 mL). The pH was adjusted to >7 with NaHCO3. The reaction mixture was extracted with EtOAc (500 mLx3). The combined organic layers were washed with brine (500 mLx3). The organic layers were concentrated, dried over Na2SO4, filtered and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (10→50% EtOAc / petroleum ether) to give 6-bromo-1-(2,2-difluoroethyl)-1H-benzo[d][1,2,3]triazole (XLIX) (5 g, 19.08 mmol, 44.5%) as a brown solid. TIFF2024539620000140.tif25153

[0318] The preparation of the intermediate (6-bromoimidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone (LII) is depicted below in Scheme 8. TIFF2024539620000141.tif54128

[0319] Step 1 A mixture of 6-bromoimidazo[1,2-a]pyridine-3-carboxylic acid (L) (0.5 g, 2.07 mmol), DIPEA (0.9 mL, 5.17 mmol), and HATU (0.79 g, 2.07 mmol) in DMF (4 mL) was stirred for 5 min. Pyrrolidine (LI) (0.32 mL, 3.18 mmol) was then added and the reaction mixture was continued to stir at room temperature for 4 h. The solvent was concentrated and the residue was partitioned between EtOAc and saturated aqueous NaHCO3, the organic layer was separated and washed with water and brine. The organic layer was dried over anhydrous Na2SO4, concentrated and dried under high vacuum to give (6-bromoimidazo[1,2-a]pyridin-3-yl)-pyrrolidin-1-ylmethanone (LII) (577 mg, 1.962 mmol, 94.6% yield) as a beige solid. ESIMS C 12 H 12 Found m / z for BrNO: 294.0 (M+H).

[0320] The preparation of the intermediate imidazo[1,2-a]pyrimidin-6-ylboronic acid (LV) is shown below in Scheme 9. TIFF2024539620000142.tif47128

[0321] Step 1 A mixture of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (LIII) (1 g, 4.52 mmol) and chloroacetaldehyde (LIV) (0.92 mL, 5.39 mmol) was dissolved in 1,4-dioxane (20 mL) and heated to 110° C. over the weekend. The reaction mixture was cooled and the solid was collected by filtration and dried under high vacuum to give imidazo[1,2-a]pyrimidin-6-ylboronic acid (LV) (650 mg, 3.989 mmol, 88.2% yield) as a brown solid which was used in the next step without purification. ESIMS found m / z 164.1 (M+H) for C6H6BN3O2.

[0322] The preparation of the intermediate 6-bromo-3-methylimidazo[1,2-a]pyrimidine (LX) is depicted below in Scheme 10. TIFF2024539620000143.tif44128

[0323] Step 1 To a mixture of propionaldehyde (LVI) (5 g, 70 mmol) in Et2O (150 mL) was added 5,5-dibromopyrimidine-2,4,6(1H,3H,5H)-trione (LVII) (9.91 g, 35 mmol) and the resulting mixture was stirred at room temperature for 16 h. After completion, the mixture was washed with petroleum ether (80 mL x 2). The organic layer was filtered and concentrated to give 2-bromopropanal (LVIII) (2.0 g, 14.6 mmol, 20.9% yield) as a yellow oil.

[0324] Step 2 To a solution of 2-bromopropanal (LVIII) (0.7 g, 5.11 mol) in DMF (20 mL) was added 5-bromopyrimidin-2-amine (LIX) (0.97 g, 5.56 mmol) under Ar at room temperature. The mixture was stirred at 100 °C for 16 h. After completion, the mixture was diluted with EtOAc and washed with brine (20 mL x 3). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude residue was purified by silica gel column chromatography (0% to 20% EtOAc / petroleum ether) to give 6-bromo-3-methylimidazo[1,2-a]pyrimidine (LX) (80 mg, 0.377 mmol, 7.4% yield) as a white solid. ESIMS found m / z 212.1 (M+H) for C7H6BrN3.

[0325] The following intermediates were prepared according to the procedures described in Scheme 10 above.

[0326] TIFF2024539620000144.tif321286-Bromo-3-ethylimidazo[1,2-a]pyrimidine (LXI): White solid (200 mg, 0.885 mmol, 19.1% yield). ESIMS found m / z 226.0 (M+H) for C8H8BrN3.

[0327] The preparation of intermediate cis-4-(methoxy-d3)cyclohexan-1-amine (LXVII) is depicted below in Scheme 11. TIFF2024539620000145.tif81149

[0328] Step 1 To a solution of cis-4-aminocyclohexan-1-ol (LXII) (5 g, 32.9 mmol), (bromomethyl)benzene (LXIII) (11.25 g, 65.8 mmol) in MeCN (80 mL) was added K2CO3 (13.64 g, 98.7 mmol). The mixture was stirred at 70 °C for 5 h. The reaction mixture was concentrated under reduced pressure to remove MeCN. The mixture was diluted with EtOAc and then extracted with EtOAc (100 mL x 3) and H2O. The combined organic layers were concentrated and the crude residue was purified by silica gel column chromatography (0% to 30% EtOAc / petroleum ether) to give cis-4-(dibenzylamino)cyclohexan-1-ol (LIV) (8.0 g, 27.08 mmol, 82.3% yield) as a white solid. ESIMS C 20 H 25 Found m / z for NO: 296.4 (M+H).

[0329] Step 2 To a solution of cis-4-(dibenzylamino)cyclohexan-1-ol (LIV) (8.0 g, 27.08 mmol) in DMPU (80 mL) was added NaH (5.98 g, 149.7 mmol) slowly under nitrogen atmosphere with continuous stirring. The reaction mixture was stirred at room temperature for 1 h. Then iodomethane-d3 (LXV) (10.85 g, 74.86 mmol) was added at room temperature over 10 min. After the addition was complete, the reaction mixture was stirred at 50 °C for 16 h. The reaction mixture was then quenched with saturated aqueous NH4Cl (300 mL) and stirred for 10 min. The mixture was diluted with EtOAc and then extracted with EtOAc (300 mL x 3) and H2O. The crude residue was purified by silica gel column chromatography (0%→20% EtOAc / petroleum ether) to give cis-N,N-dibenzyl-4-(methoxy-d3)cyclohexan-1-amine (LXVI) (6 g, 19.202 mmol, 70.9% yield) as a colorless oil. ESIMS C 21 H 24 The observed m / z for D3NO is 313.0 (M+H).

[0330] Step 3 To a solution of cis-N,N-dibenzyl-4-(methoxy-d3)cyclohexan-1-amine (LXVI) (200 mg, 0.64 mmol) in EtOH (5 mL) was added Pd(OH)2 / C (50 mg) and Pd / C (50 mg). The mixture was stirred at room temperature for 16 h. The mixture was filtered through Celite® and washed with EtOH. The reaction mixture was concentrated under reduced pressure to give cis-4-(methoxy-d3)cyclohexan-1-amine (LXVII) (76.4 mg, 0.578 mmol, 90.3% yield) as a colorless oil. TIFF2024539620000146.tif18153

[0331] The following intermediates were prepared according to the procedures described in Scheme 11 above.

[0332] TIFF2024539620000147.tif201282-((cis-4-aminocyclohexyl)oxy)ethan-1-ol (LXVIII): Colorless oil (0.5 g, 3.14 mmol, 67.4% yield). ESIMS C8H 17 Measured value for NO2: m / z 160 (M+H).

[0333] TIFF2024539620000148.tif20128cis-4-(2-Methoxyethoxy)cyclohexane-1-amine (LXIX): Colorless oil (1.5 g, 8.65 mmol, 76.6% yield). ESIMS C9H 19 Measured value for NO2: m / z 174.1 (M+H).

[0334] TIFF2024539620000149.tif22128cis-4-(2,2-difluoroethoxy)cyclohexane-1-amine (LXX): White solid (1.352 g, 7.54 mmol, 90.3% yield). ESIMS C8H 15 The observed value for F2NO is m / z 180.1 (M+H).

[0335] TIFF2024539620000150.tif16128cis-4-Ethoxycyclohexan-1-amine (LXXI): colorless oil (2 g, 13.96 mmol, 64.4% yield). TIFF2024539620000151.tif12130

[0336] TIFF2024539620000152.tif23128cis-3-(2-Methoxyethoxy)cyclobutan-1-amine (LXXII): colorless oil. TIFF2024539620000153.tif18153

[0337] The preparation of intermediate cis-4-(difluoromethoxy)cyclohexan-1-amine (LXXV) is depicted below in Scheme 12. TIFF2024539620000154.tif39152

[0338] Step 1 A solution of cis-4-(dibenzylamino)cyclohexan-1-ol (LXIV) (50 mg, 0.170 mmol), CuI (6.5 mg, 0.034 mmol) in MeCN (5 mL) was heated to 45° C. under nitrogen atmosphere for 5 min. To this mixture was added a solution of 2,2-difluoro-2-(fluorosulfonyl)acetic acid (LXXIII) (60 mg, 0.339 mmol) in MeCN (2 mL) over 10 min. The mixture was then stirred at 45° C. for 1 h. The volatile components were then removed by evaporation and the residue was diluted with EtOAc (100 mL) and 100 mL of a 1:1 mixture of water and saturated aqueous NaHCO3. The resulting biphasic mixture containing solids was filtered through a sintered glass Buchner funnel. The filtrate layers were separated and the aqueous layer was extracted with EtOAc (50 mL). The combined EtOAc layers were washed with 50 mL of a 1:1 mixture of brine and water, dried over anhydrous MgSO4, filtered, and concentrated to an oil. The crude oil was purified by silica gel chromatography (0→30% EtOAc / Hexanes). Fractions containing the product were combined and concentrated to give cis-N,N-dibenzyl-4-(difluoromethoxy)cyclohexan-1-amine (LXXIV) (25 mg, 0.072 mmol, 42.3% yield) as an oil that solidified to an off-white solid. ESIMS C 21 H 25 The observed value for F2NO is m / z 346.1 (M+H).

[0339] Step 2 To a solution of cis-N,N-dibenzyl-4-(difluoromethoxy)cyclohexan-1-amine (LXXIV) (2.8 g, 8.11 mmol) in THF (60 mL) was added Pd(OH)2 / C (1.4 g) and Pd / C (1.4 g). The mixture was stirred at room temperature for 16 h. The mixture was filtered through Celite® and washed with THF. The reaction mixture was concentrated under reduced pressure to give cis-4-(difluoromethoxy)cyclohexan-1-amine (LXXV) (1.05 g, 6.36 mmol, 78.4% yield) as a colorless oil. ESIMS C7H 13 The observed value for F2NO is m / z 166.1 (M+H).

[0340] The preparation of intermediate 1-(3,3,3-trifluoropropyl)piperidin-4-amine (LXXIX) is depicted below in Scheme 13. TIFF2024539620000155.tif45128

[0341] Step 1 tert-Butyl piperidin-4-ylcarbamate (LXXVI) (commercially available from Combi-Blocks Inc.) (1 g, 4.99 mmol) and K2CO3 (1.73 g, 12.52 mmol) were dissolved in DMF (15 mL), 1-iodo-3,3,3-trifluoropropane (LXXVII) (878 μL, 7.49 mmol) was added, and the reaction was stirred at room temperature for 16 h. The reaction mixture was poured into EtOAc and the aqueous layer was separated. The aqueous layer was extracted with EtOAc (x3), and the combined organic layers were then acidified to pH 4.5 with 1 M citric acid. The organic layer was washed three times with small amounts of water to remove unreacted SM. A sufficient amount of product remained in the organic layer, which was dried using anhydrous MgSO4 and concentrated under reduced pressure to give the product tert-butyl N-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]carbamate (LXXVIII) (861 mg, 2.906 mmol, 58.2% yield) as a white solid. ESIMS C 13 H 23 The measured value for F3N2O2 is m / z 297.2 (M+H).

[0342] Step 2 tert-Butyl N-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]carbamate (LXXVIII) (200 mg, 0.670 mmol) was dissolved in DCE (3.2 mL), TFA (800 μL, 10.38 mmol) was added, and the reaction was stirred at room temperature for 30 min. The reaction mixture was blown to dryness and excess TFA was removed under high vacuum to give the crude intermediate 1-(3,3,3-trifluoropropyl)piperidin-4-amine (LXXIX) (209 mg, 0.674 mmol, 99.8% yield) as a white semi-solid, which was used without further purification. ESIMS C8H 15 The observed value of F3N2 is m / z 197.1 (M+H).

[0343] The preparation of the intermediate N-(trans-4-aminocyclohexyl)acetamide (LXXXII) is depicted below in Scheme 14. TIFF2024539620000156.tif35128

[0344] Step 1 To a stirred solution of tert-butyl N-(4-aminocyclohexyl)carbamate (LXXX) (commercially available from Combi-Blocks Inc.) (0.6 g, 2.8 mmol) in DCM (6 mL) was added TEA (1.2 mL, 8.61 mmol). Acetyl chloride (LXXXI) (0.22 mL, 3.09 mmol) was then added slowly and the reaction mixture was stirred at room temperature for 16 h. The solvent was removed and the crude material was dissolved in EtOAc, washed with 1M NaOH, brine, dried over anhydrous MgSO4 and finally concentrated. The product was dissolved in EtOH (2 mL) and 4M HCl (1 mL). The solution was stirred at room temperature for 2 h and then evaporated to dryness to give the HCl salt of N-(4-aminocyclohexyl)acetamide (LXXXII) (480 mg, 2.49 mmol, 89.0% yield) as a white solid. ESIMS C8H 16 The observed value for NO is m / z 157.05 (M+H).

[0345] The preparation of intermediate cis-4-amino-N,N-dimethylcyclohexane-1-carboxamide (LXXXIV) is shown below in Scheme 15. TIFF2024539620000157.tif26128

[0346] Step 1 To a stirred solution of 4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid (LXXXIII) (commercially available from Combi-Blocks Inc.) (0.3 g, 1.23 mmol) in DMF (6 mL) was added DIPEA (0.65 mL, 3.73 mmol) and HATU (0.7 g, 1.85 mmol). The reaction was stirred at room temperature for 5 min. Dimethylamine (0.92 mL, 1.84 mmol) was added and the reaction was heated to 90 C for 16 h. The reaction was concentrated and dissolved in EtOH (2 mL) and 4M HCl in dioxane (1 mL). The mixture was stirred at room temperature for 2 h and concentrated under reduced pressure to give the HCl salt of 4-amino-N,N-dimethylcyclohexane-1-carboxamide (LXXXIV) (280 mg, 1.355 mmol, 109.9% yield) as a light brown sticky solid. ESIMS C9H 18 Measured value for NO: m / z 171.15 (M+H).

[0347] The following intermediates were prepared according to the procedures described in Scheme 15 above.

[0348] TIFF2024539620000158.tif23128trans-4-Amino-N,N-dimethylcyclohexane-1-carboxamide (LXXXV): Light brown viscous solid (290 mg, 1.403 mmol, 113.8% yield). ESIMS C9H 18 Measured value for NO: m / z 171.1 (M+H).

[0349] Example 1 The preparation of N-(cyclopropylmethyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (16) is shown below in Scheme 16. TIFF2024539620000159.tif100150

[0350] Step 1 To a solution of 5-bromo-2-(methylthio)pyrrolo[2,1-f][1,2,4]triazine (VII) (commercially available from Combi-Blocks Inc.) (4.0 g, 15.59 mmol) in DCM (80 mL) was added m-CPBA (3.22 g, 18.66 mmol) at 0° C. The mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with saturated aqueous NaSO at 0° C., diluted with H0 (50 mL) and extracted with EtOAc (200 mL). The combined organic layers were concentrated to give a residue. The aqueous phase was concentrated, washed with DCM / MeOH (200 mL / 10 mL) and filtered to give a residue. The combined residues were purified by reverse phase chromatography (C18-I, Regular C18 20-40 μm, 120 g, 40→45% MeCN / 0.1% formic acid in HO) to give 5-bromo-2-(methylsulfinyl)pyrrolo[2,1-f][1,2,4]triazine (VIII) (1.5 g, 5.767 mmol, 37%) as a yellow solid. TIFF2024539620000160.tif18153

[0351] Step 2 A solution of 5-bromo-2-(methylsulfinyl)pyrrolo[2,1-f][1,2,4]triazine (VIII) (400 mg, 1.55 mmol), imidazo[1,2-a]pyridin-6-ylboronic acid (LXXXVI) (commercially available from Synthonix Corporation) (301.2 mg, 1.86 mmol), PCy3 (86.8 mg, 0.31 mmol), Pd2(dba)3 (141.8 mg, 0.155 mmol), and K3PO4 (657.2 mg, 3.1 mmol) in 1,4-dioxane / HO (6 mL / 2 mL) was irradiated in a microwave under N2 at 120 °C for 0.5 h. The reaction mixture was diluted with HO (30 mL) and extracted with EtOAc (60 mL). The combined organic layers were concentrated to give a residue. The residue was purified by reverse phase chromatography (C18-I, Regular C18, 20-40 μm, 120 g, 50% MeCN / 0.1% formic acid in HO) to give the product 5-(imidazo[1,2-a]pyridin-6-yl)-2-(methylsulfinyl)pyrrolo[2,1-f][1,2,4]triazine (LXXXVII) (240 mg, 0.807 mmol, 52.1% yield) as a yellow solid. ESIMS C 14 H 11 Found m / z for N5OS is 298 (M+H).

[0352] Step 3 A solution of 5-(imidazo[1,2-a]pyridin-6-yl)-2-(methylsulfinyl)pyrrolo[2,1-f][1,2,4]triazine (LXXXVII) (58 mg, 0.185 mmol), cyclopropylmethanamine (LXXXVIII) (40.0 mg, 0.555 mmol), and DIPEA (71.8 mg, 0.555 mmol) in DME (2 mL) was irradiated in a microwave at 180 °C for 1 h. The reaction mixture was diluted with H2O (30 mL) and extracted with EtOAc (60 mL). The combined organic layers were concentrated to give a residue. The residue was purified by preparative HPLC (Sunfire C18 21.2*250mm*10μm, 18→20% MeCN / 0.1% formic acid in H2O) to give N-(cyclopropylmethyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (16) (5.16mg, 0.017mmol, 9.2% yield) as a yellow solid. TIFF2024539620000161.tif25153

[0353] Example 2 The preparation of (R)-5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (219) is shown below in Scheme 17. TIFF2024539620000162.tif42150

[0354] Step 1 (R)-1,1,1-trifluoropropan-2-amine (LXXXIX) (433.7 mg, 0.29 mmol) and Cs2CO3 (945.4 mg, 2.9 mmol) were dissolved in DMSO (2 mL) and stirred for 30 min. To this mixture was added 5-bromo-2-(methylsulfinyl)pyrrolo[2,1-f][1,2,4]triazine (VIII) (150 mg, 0.58 mmol) and pyridine (229.39 mg, 2.9 mmol). The resulting mixture was sealed and irradiated in a microwave at 180 °C for 1.5 h. The reaction mixture was then cooled to room temperature and diluted with EtOAc (30 mL). The solution was washed with water (30 mL) and the aqueous portion was extracted with EtOAc (30 mL). The combined organic extracts were washed with brine (30 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give the crude product, which was purified by preparative TLC (16.7% EtOAc / petroleum ether) to give (R)-5-bromo-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (XC) (58 mg, 0.187 mmol, 64.5% yield) as a yellow solid. ESIMS found m / z 309.0 for C9H8BrF3N4 ( 79 BrM+H).

[0355] Step 2 The procedure shown in Example 3, Scheme 18, step 2 was followed to provide (R)-5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (219) (20.91 mg, 0.060 mmol) as a yellow solid. TIFF2024539620000163.tif25153

[0356] Example 3 The preparation of 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (280) is shown below in Scheme 18. TIFF2024539620000164.tif43150

[0357] Step 1 A solution of 5-bromo-2-(methylsulfinyl)pyrrolo[2,1-f][1,2,4]triazine (VIII) (150 mg, 0.58 mmol), tetrahydro-2H-pyran-4-amine (XCI) (293.3 mg, 2.9 mmol), and pyridine (225 μL, 2.9 mmol) in DMSO (3 mL) was sealed and irradiated in a microwave at 180 °C for 1.5 h. The reaction mixture was then cooled to room temperature and diluted with EtOAc (30 mL). The solution was washed with water (30x3 mL) and the aqueous portion was extracted with EtOAc (30x3 mL). The combined organic extracts were washed with brine (30x3 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give a crude residue. The residue was purified by preparative TLC (20% EtOAc / petroleum ether) to give 5-bromo-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (XCII) (220 mg, 0.740 mmol, >100% yield) as a yellow solid. ESIMS C 11 H 13 The measured value of BrNO is m / z 297.0 ( 79 BrM+H).

[0358] Step 2 A solution of 5-bromo-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (XCII) (190 mg, 0.64 mmol), imidazo[1,2-a]pyrimidin-6-ylboronic acid (LV) (1.04 g, 6.4 mmol), PCy3 (71.8 mg, 0.26 mmol), Pd2(dba)3 (117.1 mg, 0.13 mmol), and K3PO4 (407.6 mg, 1.92 mmol) in dioxane / water (12 mL, 3:1 ratio) was sealed and irradiated in a microwave at 120 °C for 30 min. The reaction mixture was then cooled to room temperature and diluted with EtOAc (30x3 mL). The solution was washed with water (30x3 mL) and the aqueous portion was extracted with EtOAc (30x3 mL). The combined organic extracts were washed with brine (30x3 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product, which was purified by preparative TLC (6.25% MeOH / DCM -> 50% EtOAc / petroleum ether) to yield 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (280) (25.1 mg, 0.075 mmol, 11.7% yield) as a yellow solid. TIFF2024539620000165.tif31153

[0359] Example 4 The preparation of 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (642) is shown below in Scheme 19. TIFF2024539620000166.tif62151

[0360] Step 1 A mixture of 2-fluoro-2-methylpropan-1-amine hydrochloride (XCIII) (290 mg, 2.26 mmol), 5-bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (350 mg, 1.51 mmol), and DIPEA (1.2 mL, 6.89 mmol) in 1,4-dioxane (4 mL) was heated to 110° C. for 16 h. The reaction mixture was concentrated and the residue was partitioned between CHCl3 / water, the organic layer was separated, washed with brine solution, dried over anhydrous Na2SO4, the solvent was concentrated and dried under high vacuum to give the crude product 5-bromo-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (XCIV) (435 mg, 1.52 mmol, 100.6% yield), which was used in the next step without purification. ESIMS C 10 H 12 The measured value of BrFN4 was m / z 287.0 ( 79 BrM+H).

[0361] Steps 2 - 3 A mixture of 6-bromo-1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridine (XV) (100 mg, 0.370 mmol), bis(pinacolato)diboron (100 mg, 0.400 mmol), KOAc (110 mg, 1.1 mmol), and Pd(dppf)Cl2 (100 mg, 0.020 mmol) was taken up in monoglyme (1.5 mL), the mixture was purged with N2 for 2 min, the vial was sealed, and heated to 95 °C overnight. LCMS indicated completion of the reaction and formation of the boronic acid.

[0362] To the mixture was added 5-bromo-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazine-2-amine (XCIV) (70 mg, 0.240 mmol), Pd(dppf)Cl2 (100 mg, 0.020 mmol), and 2N K3PO4 solution (0.37 mL, 0.750 mmol), purged with N2 for 2 min, and the mixture was heated to 95 °C for 5 h. The organic layer was separated, absorbed onto silica gel, and purified by ISCO (0→6% 7N NH3MeOH / CHCl3). Pure fractions were combined, triturated with diethyl ether, sonicated, and the solid collected by filtration to give 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (642) (37 mg, 0.092 mmol, 37.6% yield) as a yellow solid. TIFF2024539620000167.tif31153

[0363] Example 5 The preparation of N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1771) is shown below in Scheme 20. TIFF2024539620000168.tif99153

[0364] Step 1 A mixture of DIPEA (0.79 mL, 4.52 mmol), 5-bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (350 mg, 1.51 mmol), and tert-butyl 6-amino-2-azaspiro[3.3]heptane-2-carboxylate (XCV) (480 mg, 2.26 mmol) in 1,4-dioxane (4 mL) was heated to 110° C. for 16 h. The reaction mixture was concentrated and the residue was partitioned between DCM / water, the organic layer was separated, washed with brine solution, dried over anhydrous Na2SO4, the solvent was concentrated and dried under high vacuum to give the crude product tert-butyl 6-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (XCVI) (630 mg, 1.54 mmol, 102.5% yield), which was used in the next step without purification. ESIMS C 17 H 22 BrNO2 measured m / z 352.1 (M+H- t Bu).

[0365] Step 2 A mixture of tert-butyl 6-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (XCVI) (620 mg, 1.51 mmol), 2N aqueous KPO (4.44 mL, 8.88 mmol), and Pd(dppf)Cl (60 g, 0.080 mmol) was taken in 1,4-dioxane (8 mL) and quinoline-6-boronic acid (XCVII) (520 mg, 3.01 mmol) was added. The reaction mixture was purged with N gas for 5 min, the vial was sealed, and heated at 95 °C overnight. The solvent was added to saturated aqueous NaHCO3, the solid was collected by filtration, and the crude product was purified by ISCO (4% 7N NH3MeOH / CHCl3) to give tert-butyl 6-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (XCVIII) (588 mg, 1.29 mmol, 85.5% yield) as a yellow solid. ESIMS C 26 H 28 The measured value for N6O2 is m / z 457.3 (M+H).

[0366] Step 3 To a stirred solution of tert-butyl 6-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (XCVIII) (590 mg, 1.29 mmol) in DCM (10 mL) was added TFA (3.8 mL, 49.3 mmol) and the mixture was stirred at room temperature for 3 h. The mixture was concentrated, basified with 2N NH3MeOH solution, and purified by column chromatography (0→8% 7N NH3MeOH solution / CHCl3) to give 5-(quinolin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (XCIX) (410 mg, 1.15 mmol, 89.3% yield) as a yellow solid. ESIMS C 21 H 20 Found m / z for N6: 357.2 (M+H).

[0367] Step 4 To a stirred solution of 5-(quinolin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (XCIX) (100 mg, 0.280 mmol) in DCE (1 mL) and EtOH (0.125 mL) was added isobutyraldehyde (C) (0.26 mL, 2.81 mmol). The reaction mixture was stirred for 30 min and NaBH(OAc)3 (150 mg, 0.700 mmol) was added. The reaction mixture was stirred at room temperature for 16 h. The reaction was quenched with saturated aqueous NaHCO3. Extracted with DCM. The organic layer was washed with brine and dried over MgSO4. Concentrated. Purification by column chromatography (100% CHCl3 → 6% 7N NH3MeOH solution / CHCl3) gave 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1771) (20 mg, 0.048 mmol, 18.2% yield) as a brown solid. TIFF2024539620000169.tif31153

[0368] Example 6 The preparation of 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(morpholinomethyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1842) is shown below in Scheme 21. TIFF2024539620000170.tif88153

[0369] Step 1 A mixture of 5-bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (200 mg, 0.860 mmol), (cis-4-aminocyclohexyl)methanol HCl salt (CI) (commercially available from Combi-Blocks Inc.) (215 mg, 1.3 mmol), and DIPEA (0.44 mL, 2.53 mmol) in DMSO (1 mL) was heated to 110° C. for 16 h. The reaction mixture was concentrated. The residue was purified by silica gel column chromatography (0→00% EtOAc / hexanes) to yield (cis-4-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanol (CII) (203.9 mg, 0.627 mmol, 72.9% yield) as a tan solid. TIFF2024539620000171.tif25153

[0370] Step 2 To a solution of (cis-4-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanol (CII) (180 mg, 0.550 mmol) in DCM (4 mL) at 0° C. was added MsCl (43 uL, 0.560 mmol) and TEA (231 μL, 1.66 mmol). The reaction was allowed to warm to room temperature and stirred for 2 h. The reaction was evaporated onto Celite® and purified by silica gel column chromatography (0→100% EtOAc / Hexanes) to yield ((cis-4-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methyl methanesulfonate (CIII) (182 mg, 0.451 mmol, 81.5% yield) as an off-white solid. TIFF2024539620000172.tif25153

[0371] Step 3 A solution of ((cis-4-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methyl methanesulfonate (CIII) (60 mg, 0.150 mmol) in morpholine (1 mL, 11.59 mmol) was heated to 80 °C for 20 h. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (0 → 5% MeOH / CHCl3) to give 5-bromo-N-(cis-4-(morpholinomethyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CIV) (73 mg, 0.185 mmol, 124.4% yield) as an off-white solid. ESIMS C 17 H 24 Found m / z for BrNO: 394.1 (M+H).

[0372] Steps 4 - 5 5-Chloro-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (XXXIV) (50 mg, 0.220 mmol), Pd(dppf)Cl2 (17 mg, 0.020 mmol), bis(pinacolato)diboron (82 mg, 0.320 mmol), and KOAc (63 mg, 0.640 mmol) were suspended in dioxane (4 mL). The reaction mixture was degassed with N2 and then stirred at 90 °C for 5 h. After the reaction was cooled to room temperature, 5-bromo-N-(cis-4-(morpholinomethyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CIV) (73 mg, 0.190 mmol), aqueous Na2CO3 (0.69 mL, 0.650 mmol), Pd(dppf)Cl2 (17 mg, 0.020 mmol), and monoglyme (4 mL) were added. The reaction was heated to 90 °C for 16 h. The reaction was evaporated onto Celite® and purified by silica gel column chromatography (0→50% MeOH / CHCl3) to give 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(morpholinomethyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1842) (38 mg, 0.074 mmol, 34.5% yield) as a light brown solid. TIFF2024539620000173.tif38153

[0373] Example 7 The preparation of azetidin-1-yl(cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanone (1896) is shown below in Scheme 22. TIFF2024539620000174.tif95156

[0374] Step 1 A mixture of DIPEA (1.35 mL, 7.75 mmol), 5-bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (600 mg, 2.58 mmol), and methyl 4-aminocyclohexane-1-carboxylate (CV) (commercially available from Combi-Blocks Inc.) (490 mg, 3.1 mmol) in 1,4-dioxane (10 mL) was heated to 110° C. for 16 h. The reaction was concentrated and purified by column chromatography (0→2% MeOH / CHCl3) (12 g silica gel) to give methyl 4-[(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino]cyclohexane-1-carboxylate (CVI) (729 mg, 2.064 mmol, 80.0% yield) as a light brown sticky solid. ESIMS C 14 H 17 The measured value of BrN4O2 is m / z 353.1 (M- t Bu+H).

[0375] Steps 2 - 3 A microwave vial was charged with a solution of 5-chloro-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (XXXIV) (720 mg, 3.1 mmol), bis(pinacolato)diboron (1.05 g, 4.13 mmol), KOAc (0.91 g, 9.29 mmol), and Pd(dppf)Cl (0.13 g, 0.15 mmol) in 1,4-dioxane (15 mL). The reaction mixture was heated to 90° C. for 16 h, after which methyl 4-[(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino]cyclohexane-1-carboxylate (CVI) (730 mg, 2.06 mmol), 2N aqueous K3PO4 (3.3 mL, 6.6 mmol), and Pd(dppf)Cl2 (130 mg, 0.15 mmol) were added. The reaction was stirred at 90° C. for an additional 8 h. The reaction mixture was concentrated and purified by column chromatography (0→8% MeOH / CHCl3) (silica gel 24 g) to give methyl 4-[[5-[3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]cyclohexane-1-carboxylate (CVII) (765 mg, 1.629 mmol, 78.9% yield) as an amber viscous solid. ESIMS C 23 H 25 The observed value for F2N7O2 is m / z 470.2 (M+H).

[0376] Step 4 To a mixture of water (3 mL) and THF (12 mL) was added methyl 4-[[5-[3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]cyclohexane-1-carboxylate (CVII) (729 mg, 1.55 mmol) followed by LiOH (1.4 mL, 2.8 mmol). The reaction was stirred at room temperature for 16 h. Concentrated HCl (2.9 mL, 2.9 mmol) was added to neutralize the reaction. The reaction mixture was stripped and evaporated onto Celite® and the sample was purified on reverse phase C18 silica gel (0→20% MeCN / water with 0.1% formic acid). The fractions containing the compound were lyophilized (frozen at -78°C) to yield 4-[[5-[3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]cyclohexane-1-carboxylic acid (CVIII) (450 mg, 0.988 mmol, 63.6% yield) as an orange-brown solid. ESIMS C 22 H 23 The observed value for F2N7O2 is m / z 456.2 (M+H).

[0377] Step 5 To a stirred solution of 4-[[5-[3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]cyclohexane-1-carboxylic acid (CVIII) (50 mg, 0.1 mmol) in DCM (1 mL) was added DIPEA (0.07 mL, 0.4 mmol) and HATU (60 mg, 0.15 mmol). The reaction was stirred at room temperature for 5 min. Azetidine hydrochloride (CIX) (20 mg, 0.2 mmol) was then added and the reaction was stirred at room temperature for 16 h. The reaction mixture was concentrated and purified by column chromatography (0→8% 7N NH3MeOH solution / chloroform) (silica gel 8 g) to obtain azetidin-1-yl (cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanone (1896) (7 mg, 0.014 mmol, 14.3% yield) as a yellow solid. TIFF2024539620000175.tif45153

[0378] Example 8 The preparation of 1-(7-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonan-2-yl)ethan-1-one (1899) is shown below in Scheme 23. TIFF2024539620000176.tif92155

[0379] Step 1 A mixture of 5-bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (200 mg, 0.860 mmol), tert-butyl 7-amino-2-azaspiro[3.5]nonane-2-carboxylate (CX) (commercially available from A2B Chem LLC) (311.9 mg, 1.3 mmol), and DIPEA (0.44 mL, 2.53 mmol) in DMSO (1 mL) was heated to 110° C. for 16 h. The reaction mixture was concentrated under high vacuum. The residue was purified by silica gel column chromatography (0→100% EtOAc / hexanes) to give tert-butyl 7-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonane-2-carboxylate (CXI) (2.185 mg, 0.501 mmol, 58.2% yield) as a tan solid. ESIMS C 19 H 26 The measured value of BrN5O2 is m / z 380.1 (M- t Bu+H).

[0380] Steps 2 - 3 5-Chloro-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (XXXVI) (100 mg, 0.430 mmol), Pd(dppf)Cl2 (35 mg, 0.040 mmol), bis(pinacolato)diboron (164 mg, 0.650 mmol), and KOAc (127 mg, 1.29 mmol) were suspended in dioxane (4 mL). The reaction mixture was degassed with N2 and then stirred at 90 °C for 5 h. After the reaction was cooled to room temperature, tert-butyl 7-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonane-2-carboxylate (CXI) (124 mg, 0.280 mmol), aqueous Na2CO3 (1.3 mL, 1.3 mmol), Pd(dppf)Cl2 (35 mg, 0.040 mmol), and DME (4 mL) were added. The reaction was heated to 90 °C for 16 h. The reaction mixture was evaporated onto Celite® and purified by silica gel column chromatography (0→50% MeOH / CHCl3) to give tert-butyl 7-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonane-2-carboxylate (CXII) (133 mg, 0.241 mmol, 55.7% yield) as a yellow solid. ESIMS C 28 H 34 The measured value for F2N8O2 is m / z 553.3 (M+H).

[0381] Step 4 To a solution of TFA (1 mL, 12.98 mmol) in DCE (4 mL) was added tert-butyl 7-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonane-2-carboxylate (CXII) (133 mg, 0.240 mmol) and stirred at room temperature for 1 hour. The solvent was removed and the residue was purified by silica gel column chromatography (0→10% 7N NH3MeOH solution / CHCl3) to give 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-azaspiro[3.5]nonan-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CXIII) (112 mg, 0.248 mmol, 102.8% yield) as a light yellow solid. ESIMS C 23 H 26 The observed value for F2N8 is m / z 453.2 (M+H).

[0382] Step 5 To a solution of 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-azaspiro[3.5]nonan-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CXIII) (55 mg, 0.120 mmol) in DMF (1.2 mL) was added HOAc (8 μL, 0.140 mmol), followed by HATU (60 mg, 0.160 mmol) and DIPEA (64 μL, 0.370 mmol). The solution was stirred at room temperature for 16 h. Water (40 mL) was added and the solution was extracted with EtOAc. The reaction was evaporated onto Celite® and purified by silica gel column chromatography (0→100% EtOAc / Hexane). The compound was still not pure by NMR. The crude product was dissolved in DCM, washed with saturated aqueous NaHCO3, and then repurified using silica gel column chromatography (0→100% EtOAc / hexanes) to give 1-(7-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonan-2-yl)ethan-1-one (1899) (33 mg, 0.067 mmol, 54.9% yield) as a yellow solid. TIFF2024539620000177.tif38153

[0383] Example 9 The preparation of 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-3-fluoro-1-isobutylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1909) is shown below in Scheme 24. TIFF2024539620000178.tif102153

[0384] Step 1 To a solution of 5-bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (200 mg, 0.860 mmol) and tert-butyl (3R,4S)-4-amino-3-fluoropiperidine-1-carboxylate (CXIV) (commercially available from Sunshine Chemlab, Inc.) (282 mg, 1.29 mmol) in DMSO (1 mL) was added DIPEA (450 μL, 2.58 mmol). The reaction was stirred at 120° C. for 16 h. The reaction mixture was then added to water and EtOAc and the organic layer was separated. The aqueous layer was extracted with EtOAc (x3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo to give the crude product tert-butyl (3R,4S)-4-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-3-fluoropiperidine-1-carboxylate (CXV) (457 mg, 1.103 mmol, 128% yield) as a fluffy brown solid which was used without further purification. ESIMS C 16 H 21 The measured value of BrFN5O2 is m / z 358.1 (M- t Bu+H).

[0385] Step 2 To a solution of tert-butyl (3R,4S)-4-((5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-3-fluoropiperidine-1-carboxylate (CXV) (356 mg, 0.860 mmol) in DCE (2.7 mL) was added TFA (300 μL, 3.89 mmol). The reaction was stirred at room temperature for 3 h. The reaction mixture was blown to dryness and excess TFA was removed under high vacuum to give the crude intermediate 5-bromo-N-((3R,4S)-3-fluoropiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CXVI) (270 mg, 0.859 mmol, 100% yield) as a brown semi-solid which was used without further purification. ESIMS C 11 H 13 The measured m / z for BrFN5 is 314.0 (M+H).

[0386] Step 3 To a solution of 5-bromo-N-((3R,4S)-3-fluoropiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CXVI) (135 mg, 0.430 mmol) in MeOH (3 mL) was added HOAc (50 μL, 0.870 mmol) and isobutyraldehyde (CXVII) (78 μL, 0.850 mmol). The reaction was stirred at room temperature for 20 min. NaBH(OAc)3 (228 mg, 1.08 mmol) was added and the reaction was stirred for 10 min. LCMS showed partial conversion, therefore NaBH(OAc)3 (228 mg, 1.08 mmol) was added at 5 min intervals (3 additions) until completion was confirmed by LCMS. The reaction was evaporated onto Celite® and purified by reverse phase chromatography (0→20% MeCN / 0.1% formic acid in HO) to give 5-bromo-N-((3R,4S)-3-fluoro-1-isobutylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CXVIII) (33 mg, 0.089 mmol, 20.7% yield) as a brown semi-solid. ESIMS C 15 H 21 The observed value for BrFN5 is m / z 370.1 (M+H).

[0387] Step 4 5-Chloro-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (XXXIV) (1 g, 4.32 mmol), bis(pinacolato)diboron (1.75 g, 6.89 mmol), Pd(dppf)Cl2 (176 mg, 0.220 mmol), and KOAc (1.28 g, 13.04 mmol) were dissolved in dry DMF (30 mL) and the reaction was sonicated and degassed with Ar for 5 min. The reaction was stirred at 100 °C for 16 h. The reaction mixture was cooled and concentrated in vacuo to give a black solid. The crude product was purified by C18Aq reverse phase column chromatography (0 → 11% MeCN / 0.1% formic acid in HO). The appropriate fractions were collected and evaporated under high vacuum to give (3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)boronic acid (CXIX) (543 mg, 2.253 mmol, 52.2% yield) as a fluffy yellow solid, which was stored at -20 °C. ESIMS C9H 10 Measured value for BF2N3O2: m / z 242.1 (M+H).

[0388] Step 5 To a suspension of 5-bromo-N-((3R,4S)-3-fluoro-1-isobutylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CXVIII) (32 mg, 0.090 mmol), (3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)boronic acid (CXIX) (31 mg, 0.130 mmol), and Pd(dppf)Cl2 (3 mg, 0 mmol) in dioxane (1.5 mL) was added aqueous Na2CO3 (274 μL, 0.260 mmol). The reaction was sonicated and degassed with Ar for 5 min, then heated to 100 °C for 16 h. The reaction mixture was purified by column chromatography (0 → 10% 7.0 M NH3MeOH solution / CHCl3). The compound was further purified by reverse phase chromatography (0→17% MeCN / 0.1% formic acid in HO). The appropriate fractions were collected, added to saturated aqueous NaHCO3 and extracted with DCM (x3). The combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo to give 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-3-fluoro-1-isobutylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1909) (15 mg, 0.031 mmol, 35.7% yield) as a yellow solid. TIFF2024539620000179.tif38153

[0389] Example 10 The preparation of 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-4-fluoro-1-(oxetan-3-yl)pyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1944) is shown below in Scheme 25. TIFF2024539620000180.tif95149

[0390] Step 1 5-Bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (1.5 g, 6.45 mmol), [3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]boronic acid (CXX) (1.63 g, 6.78 mmol), Pd(OAc)2 (45 mg, 0.2 mmol), and QPhos (270 mg, 0.38 mmol) were dissolved in dry 1,4-dioxane (35 mL) and purged with Ar for 5 min. 2N aqueous K3PO4 (6.45 mL, 12.9 mmol) was added and the reaction was purged with Ar for an additional 2 min. The reaction was then heated to 80° C. for 30 min. DCM and saturated aqueous NH4Cl were added to the reaction mixture and the organic layer was separated. The aqueous layer was extracted with DCM (x3) and the combined organic layers were dried (anhydrous MgSO4) and concentrated in vacuo to give an orange solid. The crude product was purified by column chromatography (0->100% EtOAc / Hexanes) followed by (0->6% 7.0M NH3 in MeOH / CHCl3). The appropriate fractions were combined and concentrated in vacuo to give an orange solid. The solid was triturated with MeOH, filtered and washed with MeOH. The product 5-(2-chloropyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (1.79 g, 5.133 mmol, 79.5% yield) was collected as a yellow solid. The filtrate was concentrated under reduced pressure to give additional 5-(2-chloropyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (CXXI) (481 mg, 1.379 mmol, 21.4% yield) as an orange solid (60% purity) which was used without further purification. ESIMS C 15 H 11 Found m / z for ClF2N6: 349.1 (M+H).

[0391] Step 2 5-(2-chloropyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (CXXI) (150 mg, 0.43 mmol) and tert-butyl (3S,4R)-3-amino-4-fluoropyrrolidine-1-carboxylate (CXXII) (114 mg, 0.56 mmol) were dissolved in DMSO (1 mL), DIPEA (150 μL, 0.86 mmol) was added, and the reaction was stirred at 120° C. for 24 hours. The reaction mixture was added to water and EtOAc, and the organic layer was separated. The aqueous layer was extracted with EtOAc (x3) and the combined organic layers were washed with brine, dried (anhydrous MgSO4) and concentrated in vacuo to give the crude product tert-butyl (3S,4R)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoropyrrolidine-1-carboxylate (CXXIII) (222 mg, 0.430 mmol, 99.9% yield assumed quantitative yield) as a brown semi-solid which was used without further purification. ESIMS C 24 H 27 The measured value for F3N8O2 is m / z 517.3 (M+H).

[0392] Step 3 tert-Butyl (3S,4R)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoropyrrolidine-1-carboxylate (CXXIII) (222 mg, 0.43 mmol) was dissolved in DCE (4.5 mL) and the reaction was cooled to 0° C. TFA (0.50 mL) was added and the reaction was stirred at room temperature for 16 hours. The reaction mixture was evaporated and the crude product was purified by column chromatography (0→2% 7.0 M NH3MeOH in CHCl3) to give 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-4-fluoropyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CXXIV) (138 mg, 0.331 mmol, 77.1% yield) as a yellow semi-solid. ESIMS C 19 H 19 The observed value for F3N8 is m / z 417.2 (M+H).

[0393] Step 4 To a solution of 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-4-fluoropyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (CXXIV) (138 mg, 0.33 mmol) in EtOH (3 mL) was added HOAc (95 μL, 1.66 mmol) and oxetan-3-one (CXXV) (97 μL, 1.66 mmol). The reaction was stirred at room temperature for 10 min. NaH(OAc)2 (105 mg, 0.5 mmol) was added and the reaction was stirred at room temperature for an additional 20 min. LCMS showed the formation of a by-product, therefore the reaction was heated to 65° C. for 30 min. LCMS showed further conversion. Additional oxetan-3-one (CXXV) (97 μL, 1.66 mmol) and HOAc (95 μL, 1.66 mmol) were added and stirred at room temperature for 5 min. NaH(OAc)2 (105 mg, 0.5 mmol) was added and stirred at 65° C. for 1 h. Several successive additions of reagents were made until no further conversion was observed (approximately 90%), thus stopping the reaction. The reaction mixture was adsorbed onto Celite® and purified by column chromatography (0→6% 7.0 M NH3MeOH solution / CHCl3). The product was further purified by HPLC (0→35% MeCN / H2O with 0.1% formic acid). Appropriate fractions were collected, neutralized with saturated aqueous NaHCO3 and extracted with DCM (x2). The combined organic layers were dried (anhydrous MgSO4) and concentrated in vacuo to give 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-4-fluoro-1-(oxetan-3-yl)pyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1944) (80 mg, 0.169 mmol, 51.1% yield) as a yellow solid. TIFF2024539620000181.tif45153

[0394] Example 11 The preparation of 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine (1916) and (4,4-difluorocyclohexyl)(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone (1953) is shown below in Scheme 26. TIFF2024539620000182.tif100151

[0395] Step 1 A mixture of DIPEA (1.6 mL, 9.19 mmol), 5-bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (530 mg, 2.26 mmol), and 4-amino-1-Boc-piperidine (CXXVI) (commercially available from Combi-Blocks Inc.) (540 mg, 2.71 mmol) in 1,4-dioxane (10 mL) was heated to 110° C. for 16 hours. The reaction was concentrated, dissolved in DCM, washed with water, brine, dried over anhydrous MgSO4, filtered, and concentrated to give tert-butyl 4-[(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino]piperidine-1-carboxylate (CXXVII) (940 mg, 2.372 mmol, 105.0% yield) as a light brown sticky solid, which was carried on to the next step without further purification. ESIMS C 16 H 22 Measured value for BrN5O2: m / z 396.1 (M+H).

[0396] Steps 2 - 3 A microwave vial was charged with 5-chloro-3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridine (XXXIV) (350 mg, 1.51 mmol), bis(pinacolato)diboron (510 mg, 2.02 mmol), KOAc (450 mg, 4.54 mmol), and a solution of Pd(dppf)Cl2 (60 mg, 0.08 mmol) in 1,4-dioxane (5 mL). The reaction mixture was heated to 90 °C for 16 h. tert-Butyl 4-[(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino]piperidine-1-carboxylate (CXXVII) (400 mg, 1.01 mmol), 2N aqueous KPO solution (1.6 mL, 3.2 mmol), and Pd(dppf)Cl (60 mg, 0.08 mmol) were added and stirred at 90 °C for an additional 8 h. The reaction mixture was concentrated and purified by column chromatography (0→8% MeOH / CHCl3) (silica gel 12 g) to give tert-butyl 4-[[5-[3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]piperidine-1-carboxylate (CXXVIII) (470 mg, 0.917 mmol, 90.8% yield) as an amber viscous solid. ESIMS C 25 H 30 The measured value for F2N8O2 is m / z 513.3 (M+H).

[0397] Step 4 To a solution of tert-butyl 4-[[5-[3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]piperidine-1-carboxylate (CXXVIII) (470 mg, 0.92 mmol) in DCM (5 mL) was added TFA (0.7 mL, 9.09 mmol). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated, basified with NH4MeOH solution (7N), and then purified by column chromatography (0→10% 7N NH3MeOH solution / CHCl3) (silica gel 12 g) to obtain 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazine-2-amine (1916) (220 mg, 0.533 mmol, yield 58.2%) as a yellow solid. TIFF2024539620000183.tif31153

[0398] Step 5 To a solution of 5-[3-(2,2-difluoroethyl)-2-methylimidazo[4,5-b]pyridin-5-yl]-N-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-2-amine (1916) (30 mg, 0.07 mmol) in DCM (1 mL) was added DIPEA (40 μL, 0.24 mmol) and HATU (40 mg, 0.11 mmol). The reaction was stirred at room temperature for 5 minutes. 4,4-Difluorocyclohexanecarboxylic acid (CXXIX) (10 mg, 0.09 mmol) was then added and the reaction was heated to 90° C. for 16 hours. The reaction mixture was concentrated and purified by column chromatography (0→8% 7N NH3MeOH solution / CHCl3) (silica gel 8 g) to obtain (4,4-difluorocyclohexyl)(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone (1953) (18 mg, 0.032 mmol, yield 44.3%) as a yellow solid. TIFF2024539620000184.tif52153

[0399] Example 12 The preparation of N-((1r,3r)-1-methyl-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide (1981) is shown below in Scheme 27. TIFF2024539620000185.tif90149

[0400] Step 1 To a microwave vial containing a solution of 5-bromo-2-chloropyrrolo[2,1-f][1,2,4]triazine (I) (commercially available from Advanced ChemBlocks Inc.) (500 mg, 2.15 mmol) in 1,4-dioxane (10 mL) was added DIPEA (1.12 mL, 6.43 mmol) and trans-tert-butyl N-(3-amino-1-methylcyclobutyl)carbamate (CXXX) (commercially available from PharmaBlock (USA), Inc.) (544 mg, 2.72 mmol). The reaction vial was capped and heated to 110° C. for 16 h. The reaction mixture was concentrated and purified by column chromatography (0→8% 7N NH3MeOH solution / CHCl3) (silica gel 8 g) to give tert-butyl N-[3-[(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino]-1-methylcyclobutyl]carbamate (CXXXI) (266 mg, 0.671 mmol, 31.2% yield) as a light yellow solid. ESIMS C 16 H 22 The measured value of BrN5O2 is m / z 396.1 (M- t Bu+H).

[0401] Step 2 To a stirred solution of tert-butyl N-[3-[(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino]-1-methylcyclobutyl]carbamate (CXXXI) (266 mg, 0.67 mmol) in DCM (1 mL) was added TFA (1.6 mL, 20.77 mmol). The mixture was stirred at room temperature for 1 h, concentrated, and the residue was purified by ISCO (0→8% 7N NH3MeOH / CHCl3). Pure fractions were collected, concentrated in vacuo, and dried under high vacuum to give 3-N-(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)-1-methylcyclobutane-1,3-diamine (CXXXII) (126 mg, 0.425 mmol, 63.4% yield) as a deep yellow solid. ESIMS C 11 H 14 Found m / z for BrN5: 296.05 (M+H).

[0402] Step 3 To a solution of HOAc (37 μL, 0.65 mmol), HATU (243 mg, 0.64 mmol) in DMF (200 μL) was added DIPEA (220 μL, 1.26 mmol). After stirring the mixture for 5 min, a solution of 3-N-(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)-1-methylcyclobutane-1,3-diamine (CXXXII) (146 mg, 0.49 mmol) in DMF (300 μL) was added and the reaction mixture was stirred at room temperature for 16 h. Water (10 mL) was added and the solution was extracted with EtOAc. The organic layer was separated, concentrated, absorbed onto silica gel and purified by ISCO (0→100% 7N NH3MeOH in CHCl3). The pure fractions were concentrated and dried under high vacuum to give N-[3-[(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino]-1-methylcyclobutyl]acetamide (CXXXIII) (130 mg, 0.384 mmol, 78.0% yield) as a deep yellow solid. ESIMS C 13 H 16 Found m / z for BrNO: 338.1 (M+H).

[0403] Step 4 A mixture of trans-N-[3-[(5-bromopyrrolo[2,1-f][1,2,4]triazin-2-yl)amino]-1-methylcyclobutyl]acetamide (CXXXIII) (30 mg, 0.09 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxaline (CXXXIV) (commercially available from AmBeed, Inc.) (27.3 mg, 0.11 mmol), Pd(dppf)Cl2 (3.7 mg, 0.0045 mmol), and 2N aqueous K3PO4 (130 μL, 0.26 mmol) in 1,4-dioxane (5 mL) was purged with N2 gas for 5 min. The mixture was stirred and irradiated in a microwave at 110 °C for 30 min. The reaction mixture was cooled and the organic layer was separated, concentrated and purified by column chromatography (0→7% 7N NH3MeOH solution / CHCl3) (silica gel 8 g) to give N-((1r,3r)-1-methyl-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide (1981) (14 mg, 0.036 mmol, 40.7% yield) as a yellow solid. TIFF2024539620000186.tif32153

[0404] The following compounds were prepared according to the procedures described above in Schemes 1-27.

[0405] TIFF2024539620000187.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine 2. Yellow solid (40.14 mg, 0.131 mmol). TIFF2024539620000188.tif31153

[0406] TIFF2024539620000189.tif34128N-(2-Fluoro-2-methylpropyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine3. Pale yellow solid (16 mg, 0.049 mmol, 38.3% yield). TIFF2024539620000190.tif31153

[0407] TIFF2024539620000191.tif35128N-(2,2-difluoropropyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine4. Yellow solid (9.31 mg, 0.028 mmol). TIFF2024539620000192.tif25153

[0408] TIFF2024539620000193.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine 9. Yellow solid (55.95 mg, 0.181 mmol). TIFF2024539620000194.tif25153

[0409] TIFF2024539620000195.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine11. Yellow solid (30.8 mg, 0.092 mmol). TIFF2024539620000196.tif32153

[0410] TIFF2024539620000197.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine12. Yellow solid (13.6 mg, 0.043 mmol). TIFF2024539620000198.tif25153

[0411] TIFF2024539620000199.tif33128N-(cyclopropylmethyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine16. Yellow solid (5.16 mg, 0.017 mmol). TIFF2024539620000200.tif31153

[0412] TIFF2024539620000201.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine 20. Yellow solid (14.48 mg, 0.045 mmol). TIFF2024539620000202.tif25153

[0413] TIFF2024539620000203.tif351285-(Imidazo[1,2-a]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine 21. Yellow solid (36.87 mg, 0.110 mmol). TIFF2024539620000204.tif31153

[0414] TIFF2024539620000205.tif33128N-(3,3-Difluorocyclobutyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine23. Yellow solid (4.61 mg, 0.014 mmol). TIFF2024539620000206.tif25153

[0415] TIFF2024539620000207.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine 26. Yellow solid (37.9 mg, 0.113 mmol). TIFF2024539620000208.tif31153

[0416] TIFF2024539620000209.tif33128N-(4,4-Difluorocyclohexyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine43. Yellow solid (52.2 mg, 0.142 mmol). TIFF2024539620000210.tif25153

[0417] TIFF2024539620000211.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine64. Yellow solid (1.93 mg, 0.006 mmol). TIFF2024539620000212.tif31153

[0418] TIFF2024539620000213.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine65. Yellow solid (28.58 mg, 0.093 mmol). TIFF2024539620000214.tif25153

[0419] TIFF2024539620000215.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine66. Yellow solid (38.32 mg, 0.110 mmol). TIFF2024539620000216.tif31153

[0420] TIFF2024539620000217.tif331285-(Imidazo[1,2-a]pyridin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine67. Yellow solid (7.97 mg, 0.024 mmol). TIFF2024539620000218.tif25153

[0421] TIFF2024539620000219.tif41128 (6-(2-((2-Fluoro-2-methylpropyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone 74. Yellow solid (21 mg, 0.050 mmol, 22.0% yield). TIFF2024539620000220.tif31153

[0422] TIFF2024539620000221.tif34128N-(2-Fluoro-2-methylpropyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine145. Light brown solid (18 mg, 0.055 mmol, 21.2% yield). TIFF2024539620000222.tif25153

[0423] TIFF2024539620000223.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine214. Yellow solid (12.01 mg, 0.041 mmol). TIFF2024539620000224.tif25153

[0424] TIFF2024539620000225.tif341285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine215. Yellow solid (25.06 mg, 0.082 mmol). TIFF2024539620000226.tif25153

[0425] TIFF2024539620000227.tif34128N-(2-Fluoro-2-methylpropyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine216. Yellow solid (102 mg, 0.314 mmol, 20.0% yield). TIFF2024539620000228.tif31153

[0426] TIFF2024539620000229.tif341285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine218. Yellow solid (8.99 mg, 0.027 mmol). TIFF2024539620000230.tif25153

[0427] TIFF2024539620000231.tif35128(R)-5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine219. Yellow solid (20.91 mg, 0.060 mmol). TIFF2024539620000232.tif25153

[0428] TIFF2024539620000233.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine220. Yellow solid (12.8 mg, 0.037 mmol). TIFF2024539620000234.tif25153

[0429] TIFF2024539620000235.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine221. Pale yellow solid (29 mg, 0.077 mmol, 26.0% yield). TIFF2024539620000236.tif31153

[0430] TIFF2024539620000237.tif33128(R)-5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine223. Yellow solid (28.36 mg, 0.088 mmol). TIFF2024539620000238.tif31153

[0431] TIFF2024539620000239.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine225. Pale yellow solid (43 mg, 0.135 mmol, 37.9% yield). TIFF2024539620000240.tif31153

[0432] TIFF2024539620000241.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine226. Pale yellow solid (27 mg, 0.072 mmol, 24.2% yield). TIFF2024539620000242.tif31153

[0433] TIFF2024539620000243.tif35128N-((1-fluorocyclobutyl)methyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine227. Pale yellow solid (30 mg, 0.089 mmol, 26.6% yield). TIFF2024539620000244.tif31153

[0434] TIFF2024539620000245.tif36128N-((3-fluorooxetan-3-yl)methyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine228. Yellow solid (26 mg, 0.077 mmol, 33.0% yield). TIFF2024539620000246.tif31153

[0435] TIFF2024539620000247.tif33128N-(cyclopropylmethyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine229. Yellow solid (11.82 mg, 0.039 mmol). TIFF2024539620000248.tif25153

[0436] TIFF2024539620000249.tif33128(S)-N-(1-Cyclopropylethyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine230. Yellow solid (28.31 mg, 0.089 mmol). TIFF2024539620000250.tif31153

[0437] TIFF2024539620000251.tif33128(R)-N-(1-Cyclopropylethyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine231. Yellow solid (21.29 mg, 0.067 mmol). TIFF2024539620000252.tif31153

[0438] TIFF2024539620000253.tif33128N-(2-Cyclopropyl-2,2-difluoroethyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine232. Yellow solid (3 mg, 0.008 mmol, 4.1% yield). TIFF2024539620000254.tif31153

[0439] TIFF2024539620000255.tif33128N-Cyclobutyl-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine235. Yellow solid (11.92 mg, 0.039 mmol). TIFF2024539620000256.tif25153

[0440] TIFF2024539620000257.tif33128N-(3,3-Difluorocyclobutyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine236. Yellow solid (10.03 mg, 0.029 mmol). TIFF2024539620000258.tif25153

[0441] TIFF2024539620000259.tif33128N-(3,3-Dimethylcyclobutyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine237. Yellow solid (9.7 mg, 0.029 mmol). TIFF2024539620000260.tif31153

[0442] TIFF2024539620000261.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine239. Yellow solid (3.11 mg, 0.009 mmol). TIFF2024539620000262.tif32153

[0443] TIFF2024539620000263.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine240. Yellow solid (9.17 mg, 0.027 mmol). TIFF2024539620000264.tif25153

[0444] TIFF2024539620000265.tif33128N-(cis-3-ethoxycyclobutyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine242. Brown solid (20 mg, 0.057 mmol, 11.9% yield). TIFF2024539620000266.tif31153

[0445] TIFF2024539620000267.tif321285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine244. Tan solid (12 mg, 0.032 mmol, 5.4% yield). TIFF2024539620000268.tif31153

[0446] TIFF2024539620000269.tif33128N-(4,4-Difluorocyclohexyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine256. Pale yellow solid (67 mg, 0.1814 mmol, 23.3% yield). TIFF2024539620000270.tif31153

[0447] TIFF2024539620000271.tif33128(1s,4s)-4-((5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol258. Yellow solid (37 mg, 0.102 mmol, 33.1% yield). TIFF2024539620000272.tif38153

[0448] TIFF2024539620000273.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine259. Beige solid (5 mg, 0.014 mmol, 4.5% yield). TIFF2024539620000274.tif31153

[0449] TIFF2024539620000275.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine260. Yellow solid (16.56 mg, 0.046 mmol). TIFF2024539620000276.tif31153

[0450] TIFF2024539620000277.tif33128N-(cis-4-ethoxycyclohexyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine263. Tan solid (44 mg, 0.117 mmol, 26.4% yield). TIFF2024539620000278.tif32153

[0451] TIFF2024539620000279.tif311285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine265. Yellow solid (18 mg, 0.044 mmol, 12.8% yield). TIFF2024539620000280.tif31153

[0452] TIFF2024539620000281.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine279. Yellow solid (18 mg, 0.052 mmol, 16.0% yield). TIFF2024539620000282.tif38153

[0453] TIFF2024539620000283.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine280. Yellow solid (54.78 mg, 0.163 mmol). TIFF2024539620000284.tif31153

[0454] TIFF2024539620000285.tif33128N-(6,6-Difluorospiro[3.3]heptan-2-yl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine281. Beige solid (33 mg, 0.087 mmol, 29.7% yield). TIFF2024539620000286.tif31153

[0455] TIFF2024539620000287.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine282. Light brown solid (11 mg, 0.032 mmol, 10.9% yield). TIFF2024539620000288.tif31153

[0456] TIFF2024539620000289.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine283. Yellow solid (5 mg, 0.014 mmol, 12.0% yield). TIFF2024539620000290.tif31153

[0457] TIFF2024539620000291.tif341285-(3-Chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine287. Yellow solid (16 mg, 0.045 mmol, 18.2% yield). TIFF2024539620000292.tif25153

[0458] TIFF2024539620000293.tif33128N-(2-Fluoro-2-methylpropyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine358. Yellow solid (10.71 mg, 0.032 mmol). TIFF2024539620000294.tif25153

[0459] TIFF2024539620000295.tif33128N-(4,4-Difluorocyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine398. Yellow solid (2.1 mg, 0.005 mmol). TIFF2024539620000296.tif31153

[0460] TIFF2024539620000297.tif331285-(3-Ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine429. Yellow solid (11.07 mg, 0.031 mmol). TIFF2024539620000298.tif25153

[0461] TIFF2024539620000299.tif371285-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine500. Yellow solid (34 mg, 0.085 mmol, 49.0% yield). TIFF2024539620000300.tif31153

[0462] TIFF2024539620000301.tif37128N-(2-fluoro-2-methylpropyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine571. Yellow solid (39 mg, 0.102 mmol, 39.1% yield). TIFF2024539620000302.tif25153

[0463] TIFF2024539620000303.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine642. Yellow solid (37 mg, 0.092 mmol, 37.6% yield). TIFF2024539620000304.tif31153

[0464] TIFF2024539620000305.tif38128N-(4,4-Difluorocyclohexyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine682. Tan-brown solid (8 mg, 0.018 mmol, 5.9% yield). TIFF2024539620000306.tif31153

[0465] TIFF2024539620000307.tif38128cis-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol683. Light brown solid (6 mg, 0.014 mmol, 4.4% yield). TIFF2024539620000308.tif38153

[0466] TIFF2024539620000309.tif38128cis-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol684. Deep yellow solid (16 mg, 0.036 mmol, 11.8% yield). TIFF2024539620000310.tif38153

[0467] TIFF2024539620000311.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine685. Light brown solid (46 mg, 0.104 mmol, 33.9% yield). TIFF2024539620000312.tif38153

[0468] TIFF2024539620000313.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine686. Light brown solid (42 mg, 0.095 mmol, 30.9% yield). TIFF2024539620000314.tif38153

[0469] TIFF2024539620000315.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(difluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine687. Light brown solid (7 mg, 0.015 mmol, 5.3% yield). TIFF2024539620000316.tif38153

[0470] TIFF2024539620000317.tif361285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine691. Yellow solid (23 mg, 0.047 mmol, 17.5% yield). TIFF2024539620000318.tif38153

[0471] TIFF2024539620000319.tif361285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine692. Deep yellow solid (25 mg, 0.052 mmol, 19.0% yield). TIFF2024539620000320.tif38153

[0472] TIFF2024539620000321.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine706. Light brown solid (8 mg, 0.019 mmol, 5.8% yield). TIFF2024539620000322.tif38153

[0473] TIFF2024539620000323.tif371285-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine713. Yellow solid (45 mg, 0.105 mmol, 43.0% yield). TIFF2024539620000324.tif31153

[0474] TIFF2024539620000325.tif37128N-(2-Fluoro-2-methylpropyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine784. Yellow solid (19 mg, 0.045 mmol, 19.8% yield). TIFF2024539620000326.tif38153

[0475] TIFF2024539620000327.tif371285-(2,3-Dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine855. Yellow solid (16 mg, 0.045 mmol, 18.6% yield). TIFF2024539620000328.tif25153

[0476] TIFF2024539620000329.tif371285-(3-Ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine926. Yellow solid (13 mg, 0.035 mmol, 13.5% yield). TIFF2024539620000330.tif31153

[0477] TIFF2024539620000331.tif37128N-(4,4-Difluorocyclohexyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1037. Yellow solid (19 mg, 0.044 mmol, 19.5% yield). TIFF2024539620000332.tif31153

[0478] TIFF2024539620000333.tif38128N-(2-Fluoro-2-methylpropyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1068. Yellow solid (86 mg, 0.213 mmol, 38.3% yield). TIFF2024539620000334.tif31153

[0479] TIFF2024539620000335.tif38128N-(3,3-difluorocyclobutyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1088. Yellow solid (13 mg, 0.031 mmol, 12.5% ​​yield). TIFF2024539620000336.tif31153

[0480] TIFF2024539620000337.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1091. Yellow solid (5 mg, 0.012 mmol, 4.8% yield). TIFF2024539620000338.tif31153

[0481] TIFF2024539620000339.tif38128N-(4,4-Difluorocyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1108. Yellow solid (35 mg, 0.078 mmol, 25.8% yield). TIFF2024539620000340.tif31153

[0482] TIFF2024539620000341.tif38128cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1109. Yellow solid (9 mg, 0.021 mmol, 6.5% yield). TIFF2024539620000342.tif38153

[0483] TIFF2024539620000343.tif38128(1s,4s)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol1110. Pale yellow solid (70 mg, 0.159 mmol, 51.6% yield). TIFF2024539620000344.tif38153

[0484] TIFF2024539620000345.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1111. Pale yellow solid (50 mg, 0.113 mmol, 36.8% yield). TIFF2024539620000346.tif38153

[0485] TIFF2024539620000347.tif38128N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1113. Yellow solid (32 mg, 0.067 mmol, 24.2% yield). TIFF2024539620000348.tif38153

[0486] TIFF2024539620000349.tif38128N-(cis-4-ethoxycyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1115. Yellow solid (54 mg, 0.119 mmol, 53.6% yield). TIFF2024539620000350.tif38153

[0487] TIFF2024539620000351.tif361285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1117. Yellow solid (44 mg, 0.091 mmol, 44.6% yield). TIFF2024539620000352.tif38153

[0488] TIFF2024539620000353.tif361285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1118. Yellow solid (12 mg, 0.025 mmol, 12.2% yield). TIFF2024539620000354.tif38153

[0489] TIFF2024539620000355.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1125. Brown solid (65.0 mg, 0.131 mmol, 30.3% yield). TIFF2024539620000356.tif38153

[0490] TIFF2024539620000357.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1131. Yellow solid (62 mg, 0.145 mmol, 45.1% yield). TIFF2024539620000358.tif38153

[0491] TIFF2024539620000359.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1132. Yellow solid (46.0 mg, 0.111 mmol, 33.1% yield). TIFF2024539620000360.tif38153

[0492] TIFF2024539620000361.tif36128N-(4,4-Difluorocyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1179. Yellow solid (20 mg, 0.045 mmol, 20.0% yield). TIFF2024539620000362.tif32153

[0493] TIFF2024539620000363.tif34128N-(2-fluoro-2-methylpropyl)-5-(1-methyl-1H-benzo[d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1210. Yellow solid (47 mg, 0.139 mmol, 53.0% yield). TIFF2024539620000364.tif25153

[0494] TIFF2024539620000365.tif35128N-(2-fluoro-2-methylpropyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1281. Yellow solid (19.6 mg, 0.058 mmol). TIFF2024539620000366.tif31153

[0495] TIFF2024539620000367.tif34128N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1309. Yellow solid (48.0 mg, 0.123 mmol, 35.0% yield). TIFF2024539620000368.tif38153

[0496] TIFF2024539620000369.tif34128cis-4-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1322. Tan solid (11 mg, 0.031 mmol, 9.5% yield). TIFF2024539620000370.tif38153

[0497] TIFF2024539620000371.tif34128(1s,4s)-1-Methyl-4-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1323. Yellow solid (8 mg, 0.021 mmol, 5.1% yield). TIFF2024539620000372.tif38153

[0498] TIFF2024539620000373.tif34128cis-N 1-(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine 1332. Yellow solid (335 mg, 0.935 mmol, 79.7% yield). TIFF2024539620000374.tif38153

[0499] TIFF2024539620000375.tif34128cis-N 1 ,N 1 -Dimethyl-N 4 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine 1336. Yellow solid (22 mg, 0.057 mmol, 35.2% yield). TIFF2024539620000376.tif38153

[0500] TIFF2024539620000377.tif34128N-(2-Methyl-2-azaspiro[3.3]heptan-6-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1348. Yellow solid (19 mg, 0.051 mmol, 18.3% yield). TIFF2024539620000378.tif38153

[0501] TIFF2024539620000379.tif35128N-(2-Fluoro-2-methylpropyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1352. Yellow solid (38.22 mg, 0.114 mmol). TIFF2024539620000380.tif31153

[0502] TIFF2024539620000381.tif34128N-(cis-3-Methoxycyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1375. Yellow solid (32 mg, 0.092 mmol, 36.6% yield). TIFF2024539620000382.tif31153

[0503] TIFF2024539620000383.tif34128N-(trans-3-Methoxycyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1376. Yellow solid (28.54 mg, 0.082 mmol, % yield). TIFF2024539620000384.tif31153

[0504] TIFF2024539620000385.tif34128N-(trans-3-(methoxymethyl)cyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1377. Yellow solid (37 mg, 0.103 mmol, 42.6% yield). TIFF2024539620000386.tif31153

[0505] TIFF2024539620000387.tif34128N-(4,4-Difluorocyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1392. Yellow solid (26 mg, 0.068 mmol, 30.2% yield). TIFF2024539620000388.tif31153

[0506] TIFF2024539620000389.tif34128cis-4-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1393. Beige solid (7 mg, 0.019 mmol, 6.0% yield). TIFF2024539620000390.tif38153

[0507] TIFF2024539620000391.tif34128(1s,4s)-1-Methyl-4-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1394. Yellow solid (30 mg, 0.080 mmol, 19.0% yield). TIFF2024539620000392.tif38153

[0508] TIFF2024539620000393.tif34128N-(cis-4-Methoxycyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1395. Yellow solid (62 mg, 0.166 mmol, 39.9% yield). TIFF2024539620000394.tif38153

[0509] TIFF2024539620000395.tif341285-(Quinoxalin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1418. Pale yellow solid (26 mg, 0.073 mmol, 24.9% yield). TIFF2024539620000396.tif31153

[0510] TIFF2024539620000397.tif35128N-(2-fluoro-2-methylpropyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1423. Yellow solid (52.33 mg, 0.143 mmol). TIFF2024539620000398.tif25153

[0511] TIFF2024539620000399.tif34128N-(cis-3-ethoxycyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1520. Beige solid (62 mg, 0.172 mmol, 53.5% yield). TIFF2024539620000400.tif38153

[0512] TIFF2024539620000401.tif33128N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1522. Light brown solid (51 mg, 0.131 mmol, 44.6% yield). TIFF2024539620000402.tif38153

[0513] TIFF2024539620000403.tif34128cis-4-((5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1535. Bright orange solid (4.0 mg, 0.011 mmol, 62.5% yield). TIFF2024539620000404.tif38153

[0514] TIFF2024539620000405.tif34128(1s,4s)-4-((5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol1536. Beige solid (7 mg, 0.019 mmol, 4.1% yield). TIFF2024539620000406.tif38153

[0515] TIFF2024539620000407.tif34128N-(cis-4-Methoxycyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1537. Pale yellow solid (18 mg, 0.048 mmol, 15.6% yield). TIFF2024539620000408.tif38153

[0516] TIFF2024539620000409.tif34128N-(cis-4-ethoxycyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1541. Light brown solid (61 mg, 0.157 mmol, 61.2% yield). TIFF2024539620000410.tif38153

[0517] TIFF2024539620000411.tif32128N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1543 Deep yellow solid (85 mg, 0.203 mmol, 50.0% yield). TIFF2024539620000412.tif39153

[0518] TIFF2024539620000413.tif32128N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1544. Light brown solid (16 mg, 0.038 mmol, 23.5% yield). TIFF2024539620000414.tif38153

[0519] TIFF2024539620000415.tif34128N-(cis-4-morpholinocyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1551. Yellow solid (25 mg, 0.058 mmol, 41.8% yield). TIFF2024539620000416.tif38153

[0520] TIFF2024539620000417.tif34128N-(1-Methylpiperidin-4-yl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1557. Light brown solid (50 mg, 0.139 mmol, 28.8% yield). TIFF2024539620000418.tif38153

[0521] TIFF2024539620000419.tif38128cis-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol1720. Pale yellow solid (43 mg, 0.108 mmol, 44.2% yield). TIFF2024539620000420.tif31153

[0522] TIFF2024539620000421.tif34128cis-3-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol1723. Yellow solid (14 mg, 0.042 mmol, 11.4% yield). TIFF2024539620000422.tif38153

[0523] TIFF2024539620000423.tif34128cis-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol1724. Yellow solid (16 mg, 0.048 mmol, 13.0% yield). TIFF2024539620000424.tif31153

[0524] TIFF2024539620000425.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1732. Light yellow solid (90 mg, 0.260 mmol, 71.2% yield). TIFF2024539620000426.tif31153

[0525] TIFF2024539620000427.tif341285-(Quinolin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1747. Yellow solid (45 mg, 0.126 mmol, 25.1% yield). TIFF2024539620000428.tif31153

[0526] TIFF2024539620000429.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1756. Yellow solid (20 mg, 0.050 mmol, 43.0% yield). TIFF2024539620000430.tif45153

[0527] TIFF2024539620000431.tif34128N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1771. Yellow solid (60 mg, 0.145 mmol, 51.8% yield). TIFF2024539620000432.tif45153

[0528] TIFF2024539620000433.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1780. Brown solid (20 mg, 0.048 mmol, 18.2% yield). TIFF2024539620000434.tif31153

[0529] TIFF2024539620000435.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1786. Light brown solid (35 mg, 0.071 mmol, 26.8% yield). TIFF2024539620000436.tif38153

[0530] TIFF2024539620000437.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1792. Pale yellow solid (33 mg, 0.067 mmol, 21.7% yield). TIFF2024539620000438.tif38153

[0531] TIFF2024539620000439.tif341285-(1,8-Naphthyridin-3-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1798. Yellow solid (13 mg, 0.030 mmol, 9.2% yield). TIFF2024539620000440.tif38153

[0532] TIFF2024539620000441.tif37128N-(2-Fluoro-2-methylpropyl)-5-(3-isopropyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1801. Yellow solid (24 mg, 0.063 mmol, 21.3% yield). TIFF2024539620000442.tif31153

[0533] TIFF2024539620000443.tif331285-(Imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(methoxy-d3)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1802. Pale yellow solid (61 mg, 0.167 mmol, 54.6% yield). TIFF2024539620000444.tif31153

[0534] TIFF2024539620000445.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(methoxy-d3)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1803. Pale yellow solid (50 mg, 0.113 mmol, 36.9% yield). TIFF2024539620000446.tif38153

[0535] TIFF2024539620000447.tif38128cis-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol1813. Yellow-green solid (8 mg, 0.019 mmol, 5.8% yield). TIFF2024539620000448.tif31153

[0536] TIFF2024539620000449.tif38128cis-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol1819. Yellow-green solid (13 mg, 0.031 mmol, 12.5% ​​yield). TIFF2024539620000450.tif38153

[0537] TIFF2024539620000451.tif34128cis-3-((5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol1825. Brownish orange solid (6 mg, 0.017 mmol, 5.1% yield). TIFF2024539620000452.tif38153

[0538] TIFF2024539620000453.tif33128trans-4-((5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol1828. Beige solid (22 mg, 0.061 mmol, 24.7% yield). TIFF2024539620000454.tif31153

[0539] TIFF2024539620000455.tif37128cis-4-((5-(3-isobutyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol1829. Yellow solid (18.4 mg, 0.042 mmol, 21.6% yield). TIFF2024539620000456.tif38153

[0540] TIFF2024539620000457.tif38128(R)-2-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)propan-1-ol1830. Pale yellow solid (30 mg, 0.077 mmol, 37.5% yield). TIFF2024539620000458.tif38153

[0541] TIFF2024539620000459.tif39128(R)-1-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)propan-2-ol1831. Light yellow solid (54 mg, 0.139 mmol, 46.7% yield). TIFF2024539620000460.tif31153

[0542] TIFF2024539620000461.tif39128(S)-1-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)propan-2-ol1832. Light yellow solid (48 mg, 0.124 mmol, 38.6% yield). TIFF2024539620000462.tif32153

[0543] TIFF2024539620000463.tif381281-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-methylpropan-2-ol1833. Bright yellow solid (43 mg, 0.107 mmol, 30.9% yield). TIFF2024539620000464.tif31153

[0544] TIFF2024539620000465.tif38128(cis-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)methanol1834. Light yellow solid (50 mg, 0.121 mmol, 44.9% yield). TIFF2024539620000466.tif38153

[0545] TIFF2024539620000467.tif38128trans-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol1835. Bright yellow solid (40 mg, 0.097 mmol, 45.6% yield). TIFF2024539620000468.tif31153

[0546] TIFF2024539620000469.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(7-methyl-7-azaspiro[3.5]nonan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1836. Yellow solid (44 mg, 0.086 mmol, 97.1% yield). TIFF2024539620000470.tif38153

[0547] TIFF2024539620000471.tif38128(cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanol1837. Light yellow solid (226 mg, 0.512 mmol, 59.3% yield). TIFF2024539620000472.tif38153

[0548] TIFF2024539620000473.tif38128N-(cis-4-(2,2-difluoroethoxy)cyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1838. Yellow solid (20 mg, 0.041 mmol, 20.4% yield). TIFF2024539620000474.tif38153

[0549] TIFF2024539620000475.tif381282-((cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)oxy)ethan-1-ol1839. Yellow solid (4 mg, 0.009 mmol, 4.0% yield). TIFF2024539620000476.tif39153

[0550] TIFF2024539620000477.tif38128trans-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol1840. Brownish orange solid (9 mg, 0.020 mmol, 6.6% yield). TIFF2024539620000478.tif38153

[0551] TIFF2024539620000479.tif371285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-((4-methylpiperazin-1-yl)methyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1841. Light brown solid (24 mg, 0.046 mmol, 21.2% yield). TIFF2024539620000480.tif38153

[0552] TIFF2024539620000481.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(morpholinomethyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1842. Light brown solid (38 mg, 0.074 mmol, 34.5% yield). TIFF2024539620000482.tif38153

[0553] TIFF2024539620000483.tif38128 Ethyl cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexane-1-carboxylate1843. Yellow solid (22 mg, 0.046 mmol, 8.6% yield). TIFF2024539620000484.tif38153

[0554] TIFF2024539620000485.tif38128N-(trans-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)acetamide1844. Yellow solid (7 mg, 0.015 mmol, 8.1% yield). TIFF2024539620000486.tif38153

[0555] TIFF2024539620000487.tif38128cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N-dimethylcyclohexane-1-carboxamide 1845. Yellow solid (55 mg, 0.114 mmol, 41.7% yield). TIFF2024539620000488.tif38153

[0556] TIFF2024539620000489.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methyl-2-azaspiro[3.5]nonan-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1846. Yellow solid (35 mg, 0.075 mmol, 61.7% yield). TIFF2024539620000490.tif39153

[0557] TIFF2024539620000491.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1,4-dioxaspiro[4.5]decan-8-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1847. Yellow solid (78 mg, 0.166 mmol, 48.9% yield). TIFF2024539620000492.tif31153

[0558] TIFF2024539620000493.tif441285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((4-methylmorpholin-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1848. Deep yellow solid (46 mg, 0.104 mmol, 44.6% yield). TIFF2024539620000494.tif45153

[0559] TIFF2024539620000495.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(2-fluoroethyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1849. Yellow solid (2.4 mg, 0.005 mmol, 2.4% yield). TIFF2024539620000496.tif38153

[0560] TIFF2024539620000497.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(2,2-difluoroethyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1850. Yellow solid (32 mg, 0.067 mmol, 28.1% yield). TIFF2024539620000498.tif45153

[0561] TIFF2024539620000499.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(3,3,3-trifluoropropyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1851. Yellow solid (7 mg, 0.014 mmol, 10.8% yield). TIFF2024539620000500.tif38153

[0562] TIFF2024539620000501.tif381282-(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)ethan-1-ol 1852. Light brown solid (13 mg, 0.029 mmol, 12.9% yield). TIFF2024539620000502.tif38153

[0563] TIFF2024539620000503.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1853. Yellow solid (2 mg, 0.005 mmol, 3.7% yield). TIFF2024539620000504.tif38153

[0564] TIFF2024539620000505.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1854. Yellow solid (2.5 mg, 0.006 mmol, 4.6% yield). TIFF2024539620000506.tif38153

[0565] TIFF2024539620000507.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4S)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1855. Yellow solid (4 mg, 0.009 mmol, 7.4% yield). TIFF2024539620000508.tif38153

[0566] TIFF2024539620000509.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1856. Yellow solid (4 mg, 0.009 mmol, 8.4% yield). TIFF2024539620000510.tif38153

[0567] TIFF2024539620000511.tif381281-(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)ethan-1-one1857. Yellow solid (5 mg, 0.011 mmol, 3.7% yield). TIFF2024539620000512.tif45153

[0568] TIFF2024539620000513.tif381281-(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)propan-1-one1858. Bright orange solid (5 mg, 0.011 mmol, 37.2% yield). TIFF2024539620000514.tif45153

[0569] TIFF2024539620000515.tif381281-(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)-2-methylpropan-1-one1859. Yellow solid (5 mg, 0.010 mmol, 5.1% yield). TIFF2024539620000516.tif45153

[0570] TIFF2024539620000517.tif38128 Cyclopropyl((4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone 1860. Yellow solid (19 mg, 0.040 mmol, 14.4% yield). TIFF2024539620000518.tif38153

[0571] TIFF2024539620000519.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(methylsulfonyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1861. Off-white solid (58 mg, 0.118 mmol, 55.3% yield). TIFF2024539620000520.tif38153

[0572] TIFF2024539620000521.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1862. Yellow solid (31 mg, 0.066 mmol, 28.8% yield). TIFF2024539620000522.tif45153

[0573] TIFF2024539620000523.tif38128(R)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1863. Off-white solid (48 mg, 0.116 mmol, 53.1% yield). TIFF2024539620000524.tif38153

[0574] TIFF2024539620000525.tif38128(S)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1864. Off-white solid (59 mg, 0.143 mmol, 77.1% yield). TIFF2024539620000526.tif38153

[0575] TIFF2024539620000527.tif39128(3R,4R)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)tetrahydro-2H-pyran-3-ol1865. Yellow solid (116 mg, 0.270 mmol, 84.6% yield). TIFF2024539620000528.tif45153

[0576] TIFF2024539620000529.tif39128(3S,4R)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)tetrahydro-2H-pyran-3-ol1866. Yellow solid (70 mg, 0.163 mmol, 78.5% yield). TIFF2024539620000530.tif38153

[0577] TIFF2024539620000531.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-methoxytetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1867. Off-white solid (69 mg, 0.156 mmol, 75.0% yield). TIFF2024539620000532.tif45153

[0578] TIFF2024539620000533.tif36128cis-1-Methyl-4-((5-(2-methyl-3-(2,2,2-trifluoroethyl)-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1868. Yellow solid (12.1 mg, 0.026 mmol, 13.7% yield). TIFF2024539620000534.tif31153

[0579] TIFF2024539620000535.tif381283-(5-(2-((cis-4-hydroxy-4-methylcyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-2,2-dimethylpropanenitrile1869. Yellow solid (17.2 mg, 0.038 mmol, 15.8% yield). TIFF2024539620000536.tif38153

[0580] TIFF2024539620000537.tif381281-(5-(2-((4,4-difluorocyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-2-methylpropan-2-ol1870. Yellow solid (12.2 mg, 0.027 mmol, 13.7% yield). TIFF2024539620000538.tif31153

[0581] TIFF2024539620000539.tif381282-Methyl-1-(2-methyl-5-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)-3H-imidazo[4,5-b]pyridin-3-yl)propan-2-ol1871. Yellow solid (15.9 mg, 0.038 mmol, 17.3% yield). TIFF2024539620000540.tif39153

[0582] TIFF2024539620000541.tif381282-(5-(2-((cis-4-hydroxy-4-methylcyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-N,N-dimethylacetamide 1872. Yellow solid (23.9 mg, 0.052 mmol, 25.5% yield). TIFF2024539620000542.tif38153

[0583] TIFF2024539620000543.tif401285-(3-(azetidin-3-ylmethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(4,4-difluorocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1873. Yellow solid (18.0 mg, 0.040 mmol, 34.3% yield). TIFF2024539620000544.tif38153

[0584] TIFF2024539620000545.tif40128cis-1-Methyl-4-((5-(2-methyl-3-(oxetan-3-ylmethyl)-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1875. Off-white solid (19.9 mg, 0.045 mmol, 19.8% yield). TIFF2024539620000546.tif38153

[0585] TIFF2024539620000547.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(methoxy-d3)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1876. Light brown solid (62 mg, 0.140 mmol, 41.6% yield). TIFF2024539620000548.tif38153

[0586] TIFF2024539620000549.tif38128N-(cis-4-(2,2-difluoroethoxy)cyclohexyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1877. Yellow solid (27 mg, 0.055 mmol, 20.6% yield). TIFF2024539620000550.tif38153

[0587] TIFF2024539620000551.tif371282-((cis-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)oxy)ethan-1-ol 1878. Yellow-green solid (19 mg, 0.040 mmol, 20.5% yield). TIFF2024539620000552.tif38153

[0588] TIFF2024539620000553.tif38128trans-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol1879. Yellow-green solid (38 mg, 0.086 mmol, 28.0% yield). TIFF2024539620000554.tif39153

[0589] TIFF2024539620000555.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1,4-dioxaspiro[4.5]decan-8-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1880. Bright yellow solid (36 mg, 0.077 mmol, 26.6% yield). TIFF2024539620000556.tif38153

[0590] TIFF2024539620000557.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-(2-fluoroethyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1881. Yellow solid (7 mg, 0.015 mmol, 13.1% yield). TIFF2024539620000558.tif38153

[0591] TIFF2024539620000559.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-(2,2-difluoroethyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1882. Yellow solid (18 mg, 0.038 mmol, 34.0% yield). TIFF2024539620000560.tif38153

[0592] TIFF2024539620000561.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-(3,3,3-trifluoropropyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1883. Deep yellow solid (13 mg, 0.026 mmol, 16.7% yield). TIFF2024539620000562.tif38153

[0593] TIFF2024539620000563.tif391285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1884. Deep yellow solid (16 mg, 0.036 mmol, 29.5% yield). TIFF2024539620000564.tif38153

[0594] TIFF2024539620000565.tif391285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1885. Deep yellow solid (16 mg, 0.036 mmol, 29.5% yield). TIFF2024539620000566.tif38153

[0595] TIFF2024539620000567.tif391285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3S,4S)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1886. Deep yellow solid (19 mg, 0.043 mmol, 35.1% yield). TIFF2024539620000568.tif38153

[0596] TIFF2024539620000569.tif391285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3R,4S)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1887. Deep yellow solid (16 mg, 0.036 mmol, 33.8% yield). TIFF2024539620000570.tif45153

[0597] TIFF2024539620000571.tif381281-(4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)-2-methylpropan-1-one1888. Light brown solid (5 mg, 0.010 mmol, 5.1% yield). TIFF2024539620000572.tif45153

[0598] TIFF2024539620000573.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1889. Deep yellow solid (29 mg, 0.062 mmol, 54.5% yield). TIFF2024539620000574.tif38153

[0599] TIFF2024539620000575.tif38128trans-4-((5-(1-(2,2-difluoroethyl)-1H-benzo[d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol1890. Yellow solid (5 mg, 0.012 mmol, 8.9% yield). TIFF2024539620000576.tif31153

[0600] TIFF2024539620000577.tif32128trans-1-Methyl-4-((5-(pyrazolo[1,5-a]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol1891. Yellow solid (80 mg, 0.221 mmol, 71.8% yield). TIFF2024539620000578.tif31153

[0601] TIFF2024539620000579.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1893. Yellow solid (37 mg, 0.079 mmol, 11.4% yield). TIFF2024539620000580.tif31153

[0602] TIFF2024539620000581.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1893. Yellow solid (32 mg, 0.068 mmol, 9.9% yield). TIFF2024539620000582.tif31153

[0603] TIFF2024539620000583.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-((3-fluoroazetidin-1-yl)methyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1894. Yellow solid (5.7 mg, 0.011 mmol, 22.1% yield). TIFF2024539620000584.tif38153

[0604] TIFF2024539620000585.tif38128trans-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N-dimethylcyclohexane-1-carboxamide1895. Yellow solid (8 mg, 0.017 mmol, 6.1% yield). TIFF2024539620000586.tif45153

[0605] TIFF2024539620000587.tif37128 Azetidin-1-yl (cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanone1896. Yellow solid (7 mg, 0.014 mmol, 14.3% yield). TIFF2024539620000588.tif45153

[0606] TIFF2024539620000589.tif37128N-(cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)acetamide 1898. Yellow solid (60 mg, 0.128 mmol, 72.8% yield). TIFF2024539620000590.tif38153

[0607] TIFF2024539620000591.tif381281-(7-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonan-2-yl)ethan-1-one1899. Yellow solid (33 mg, 0.067 mmol, 54.9% yield). TIFF2024539620000592.tif39153

[0608] TIFF2024539620000593.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-4-fluoro-1-methylpyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1900. Yellow solid (36 mg, 0.084 mmol, 26.3% yield). TIFF2024539620000594.tif38153

[0609] TIFF2024539620000595.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4S)-4-fluoro-1-methylpyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1901. Yellow solid (34 mg, 0.079 mmol, 24.8% yield). TIFF2024539620000596.tif38153

[0610] TIFF2024539620000597.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4R)-4-fluoro-1-methylpyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1902. Yellow solid (28 mg, 0.065 mmol, 20.4% yield). TIFF2024539620000598.tif38153

[0611] TIFF2024539620000599.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-4-fluoro-1-methylpyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1903. Yellow solid (35 mg, 0.081 mmol, 25.5% yield). TIFF2024539620000600.tif38153

[0612] TIFF2024539620000601.tif38128(3S,4R)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)tetrahydrofuran-3-ol1906. Yellow solid (80 mg, 0.193 mmol, 57.6% yield). TIFF2024539620000602.tif38153

[0613] TIFF2024539620000603.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-fluoro-1-isobutylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1908. Yellow solid (22 mg, 0.045 mmol, 55.8% yield). TIFF2024539620000604.tif38153

[0614] TIFF2024539620000605.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-3-fluoro-1-isobutylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1909. Yellow solid (15 mg, 0.031 mmol, 35.7% yield). TIFF2024539620000606.tif38153

[0615] TIFF2024539620000607.tif381281-(4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)ethan-1-one1910. Light brown solid (8 mg, 0.0178 mmol, 3.4% yield). TIFF2024539620000608.tif38153

[0616] TIFF2024539620000609.tif37128(S)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylpiperidin-2-one1911. Yellow solid (12 mg, 0.027 mmol, 67.9% yield). TIFF2024539620000610.tif38153

[0617] TIFF2024539620000611.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1912. Yellow solid (17 mg, 0.039 mmol, 62.0% yield). TIFF2024539620000612.tif38153

[0618] TIFF2024539620000613.tif37128N-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1914. Yellow solid (58 mg, 0.141 mmol, 80.0% yield). TIFF2024539620000614.tif31153

[0619] TIFF2024539620000615.tif44128(R)-N-(4,4-difluorocyclohexyl)-5-(1-((5-(1-fluoroethyl)-1,3,4-oxadiazol-2-yl)methyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1915. Beige solid (15 mg, 0.029 mmol, 16.6% yield). TIFF2024539620000616.tif31153

[0620] TIFF2024539620000617.tif371285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1916. Yellow solid (220 mg, 0.533 mmol, 58.2% yield). TIFF2024539620000618.tif38153

[0621] TIFF2024539620000619.tif38128(S)-(2,2-Difluorocyclopropyl)(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone1917. Yellow solid (9 mg, 0.017 mmol, 14.4% yield). TIFF2024539620000620.tif45153

[0622] TIFF2024539620000621.tif38128(R)-(2,2-Difluorocyclopropyl)(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone1918. Yellow solid (14 mg, 0.027 mmol, 22.4% yield). TIFF2024539620000622.tif45153

[0623] TIFF2024539620000623.tif38128N-((1r,3r)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)acetamide 1920. Yellow solid (23 mg, 0.051 mmol, 24.5% yield). TIFF2024539620000624.tif38153

[0624] TIFF2024539620000625.tif391281-((3S,4R)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoropyrrolidin-1-yl)ethan-1-one1940. Yellow solid (9 mg, 0.020 mmol, 45.4% yield). TIFF2024539620000626.tif38153

[0625] TIFF2024539620000627.tif391281-((3R,4S)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoropyrrolidin-1-yl)ethan-1-one1941. Yellow solid (8 mg, 0.018 mmol, 22.7% yield). TIFF2024539620000628.tif38153

[0626] TIFF2024539620000629.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-4-fluoro-1-(oxetan-3-yl)pyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1944. Yellow solid (80 mg, 0.169 mmol, 51.1% yield). TIFF2024539620000630.tif45153

[0627] TIFF2024539620000631.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-4-fluoro-1-(oxetan-3-yl)pyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1945. Yellow solid (59 mg, 0.125 mmol, 38.5% yield). TIFF2024539620000632.tif45153

[0628] TIFF2024539620000633.tif37128 (3,3-Difluoroazetidin-1-yl)(cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanone 1950. Yellow solid (10 mg, 0.019 mmol, 19.1% yield). TIFF2024539620000634.tif38153

[0629] TIFF2024539620000635.tif391281-((3S,4R)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-3-fluoropiperidin-1-yl)ethan-1-one1951. Yellow solid (31 mg, 0.066 mmol, 58.8% yield). TIFF2024539620000636.tif45153

[0630] TIFF2024539620000637.tif391281-((3R,4S)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-3-fluoropiperidin-1-yl)ethan-1-one1952. Yellow solid (30 mg, 0.064 mmol, 51.6% yield). TIFF2024539620000638.tif52153

[0631] TIFF2024539620000639.tif38128(4,4-Difluorocyclohexyl)(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone1953. Yellow solid (18 mg, 0.032 mmol, 44.3% yield). TIFF2024539620000640.tif51153

[0632] TIFF2024539620000641.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1954. Yellow solid (67 mg, 0.138 mmol, 38.0% yield). TIFF2024539620000642.tif52153

[0633] TIFF2024539620000643.tif391285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1955. Yellow solid (69 mg, 0.142 mmol, 40.7% yield). TIFF2024539620000644.tif52153

[0634] TIFF2024539620000645.tif381285-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-oxaspiro[3.5]nonan-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1961. Yellow solid (60 mg, 0.132 mmol, 38.5% yield). TIFF2024539620000646.tif39153

[0635] TIFF2024539620000647.tif381285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1970. White solid (6.52 mg, 0.013 mmol, 10.0% yield). TIFF2024539620000648.tif31153

[0636] TIFF2024539620000649.tif401285-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-5-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine1971. White solid (6.75 mg, 0.014 mmol, 10.3% yield). TIFF2024539620000650.tif31153

[0637] TIFF2024539620000651.tif37128cis-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol 1974. Yellow fluffy solid (27 mg, 0.06 mmol, 24.8% yield). TIFF2024539620000652.tif31153

[0638] TIFF2024539620000653.tif34128N-((1r,3r)-1-Methyl-3-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide 1980. Yellow solid (4 mg, 0.010 mmol, 11.7% yield). TIFF2024539620000654.tif38153

[0639] TIFF2024539620000655.tif34128N-((1r,3r)-1-Methyl-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide 1981. Yellow solid (14 mg, 0.036 mmol, 40.7% yield). TIFF2024539620000656.tif38153

[0640] TIFF2024539620000657.tif33128N-(trans-1-methyl-3-((5-(pyrazolo[1,5-a]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide 1983. Yellow solid (10 mg, 0.027 mmol, 22.5% yield). TIFF2024539620000658.tif31153

[0641] TIFF2024539620000659.tif341282-Methoxy-N-(trans-1-methyl-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide 1985. Yellow solid (8 mg, 0.019 mmol, 14.7% yield). TIFF2024539620000660.tif38153

[0642] Example 13 Representative compounds were screened using the assay procedure for DYRK1A kinase activity described below.

[0643] Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilutions (1:3, 11-point dose-response curves from 10 μM to 0.00016 μM) and transfer of compounds into 1536-well black-walled round-bottom plates (Corning) were performed using an ECHO 550 (Labcyte, Sunnyvale, CA).

[0644] DYRK1A kinase assay was performed using the Ser / Thr 18 Peptide Z-lyte Assay Kit (Life Technologies, a division of Thermo-Fisher) according to the manufacturer's instructions. This is a non-radioactive assay that uses fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity, expressed as the ratio of coumarin emission / fluorescein emission.

[0645] Briefly, recombinant DYRK1A kinase, ATP, and Ser / Thr peptide 18 were prepared in 1X kinase buffer at final concentrations of 0.25 μg / mL, 15 μM, and 4 μM, respectively. The mixtures were incubated with representative compounds for 1 hour at room temperature. All reactions were performed in duplicate. Unphosphorylated ("0% control") and phosphorylated ("100% control") forms of Ser / Thr 18 were used as control reactions. Additionally, an 11-point dose-response curve of staurosporine (up to 1 uM) was performed to serve as a positive compound control.

[0646] After incubation, developing reagent A was diluted in developing buffer and then added to the reaction and further incubated for 1 h at room temperature. Plates were read with Ex 400 Em 455 to detect coumarin signal and with Ex 400 Em 520 to measure signal (EnVision multilabel plate reader, PerkinElmer).

[0647] Emission ratio (Em) was calculated as the ratio of coumarin (C) luminescence signal (at 445 nm) / fluorescein (F) luminescence signal (at 520 nm). Percent phosphorylation was then calculated using the following formula: [1 - ((Em ratio x F100%) - C100%) / ((C0% - C100%) + (Em ratio x (F100% - F0%)))]. Dose-response curves were generated in Dotmatics Studies software (Bishops Stortford, UK) and inhibitory concentrations (IC 50 ) values ​​were calculated using nonlinear regression curve fitting.

[0648] Table 2 shows the measured activity of representative compounds of formula I described herein.

[0649] [Table 2] TIFF2024539620000662.tif213170

[0650] Example 14 Representative compounds were screened using the assay procedure for tau phosphorylation activity described below.

[0651] HEK293T cells (ATCC, CRL3216) cultured in DMEM (Thermo Fisher Scientific, 10566024) supplemented with 10% FBS (Corning, 35-011-CV) and penicillin / streptomycin (Thermo Fisher Scientific, 15140163) were plated at 75 cm 2 8.1x10 cells in flask 6HEK293T cells were then transiently transfected with 5 μg of DYRK1A (NM_001396) human untagged clone (OriGene, SC314641) and 2.5 μg of MAPT (441 amino acid tau gene) (NM_005910) human untagged clone (OriGene, TP313312) using Lipofectamine 3000 (Thermo Fisher Scientific, L30000015) and incubated for 20-30 h at 37 °C and 5% CO2 in a humidified incubator. After incubation, HEK293T cells were transfected with DYRK1A and MAPT expression vectors were harvested and plated at 3x10 cells / flask in BioCoat poly-D lysine coated 96-well plates (Corning, 354461). 4 Cells were seeded at 1 cell / well.

[0652] The compounds synthesized above were screened using a cellular assay procedure that assesses the reduction of tau phosphorylation at Thr212 (pThr212) described below.

[0653] Each compound was dissolved in DMSO (Sigma-Aldrich, D8418 - 100mL) as a 10 mM stock. The 10 mM stock was serially diluted 1:3 in a 10-point dose-response curve and added to cells at final concentrations ranging from 20 μM to 1.1 nM. Cells were treated with compounds in duplicate and incubated for 18-24 hours at 37°C and 5% CO2 in a humidified incubator.

[0654] After overnight compound treatment, cells were lysed with 1X Alpha Surefire Ultra lysis buffer (Perkin Elmer, ALSU-LB-100ML) supplemented with 1X Halt phosphatase inhibitor cocktail (Thermo Fisher Scientific, 78427) and 1X Halt protease inhibitor cocktail (Thermo Fisher Scientific, 78438). Lysates were spun down at 12,000g for 10 min to remove any cell debris and 5 μL of lysate was dispensed into 384-well Opti-Plates (Perkin Elmer, 6007290) for measurement of tau phosphorylation in the phosphorylated tau (Thr212) AlphaLISA assay. Donor antibody biotinylated HT7 tau (Thermo Fisher Scientific, MN1000B) and acceptor antibody pThr212 tau (Thermo Fisher Scientific, 44740G), both at a final concentration of 3 nM, were added to the cell lysates and incubated at room temperature for 1 h. After incubating the lysates with donor and acceptor antibodies, anti-rabbit IgG (Fc specific) AlphaLISA acceptor beads (Perkin Elmer, AL104C) were added at a final concentration of 10ug / mL and incubated at room temperature for 1 hour in the dark. Finally, AlphaScreen Streptavidin Donor Beads (PerkinElmer, 6760002) were added at a final concentration of 40ug / mL and incubated at room temperature for 1 hour in the dark. Plates were read on an EnVision multilabel plate reader (Perkin Elmer) at Ex = 665nm and Em = 615nm.

[0655] The phosphorylated tau (Thr212) AlphaLISA signal was used to plot and draw curve fittings and the EC values ​​for each compound were calculated using Prism (GraphPad). 50 has been confirmed.

[0656] Table 3 shows the activity of representative compounds provided herein.

[0657]

Table 3

Claims

1. A compound of formula I, or a pharmaceutically acceptable salt thereof: During the ceremony, R 1 is 1 to 10 R 3 is heteroaryl optionally substituted with R 2 is unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), -(C 1～5 alkylene) p OR 4 , 1 to 10 R 5 may be substituted with -(C 1～5 alkylene) p Heterocyclyl, 1 to 10 R 6 -heteroaryl optionally substituted with, and 1 to 12 R 7 may be substituted with -(C 1～5 alkylene) p carbocyclyl, wherein each -(C 1～5 alkylene) independently represents 1 to 5 halide and / or 1 to 3 unsubstituted -(C 1～3 alkyl); Each R 3 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), -(C 1～5 alkylene) p OR 8 , -(C 1～5 alkylene)CN, 1 to 10 R 9 may be substituted with -(C 1～5 alkylene) p Heterocyclyl, 1 to 12 R 10 -carbocyclyl, 1 to 10 R 19 may be substituted with -(C 1～5 alkylene) p Heteroaryl, -(C 1～5 alkylene) p C(=O)N(R 11 ) 2 , and -C(=O)R 12 wherein each -(C 1～5 alkylene) independently represents 1 to 5 halide and / or 1 to 3 unsubstituted -(C 1～3 alkyl); Each R 4 are independently H, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 5 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), 1 to 10 R 15 -heterocyclyl, -(C 1～5 alkylene) p OR 20 , -SO 2 R 22 , and -C(=O)R 23 wherein -(C 1～5 alkylene) is 1 to 5 halide and / or 1 to 3 unsubstituted -(C 1～3 alkyl); Alternatively, two R attached to the same carbon atom 5 together to form a carbonyl group; Each R 6 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), and -OMe; Each R 7 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), -N(R 13 ) 2 , -(C 1～5 alkylene) p OR 14 , 1 to 10 R 15 may be substituted with -(C 1～5 alkylene) p Heterocyclyl, -C(=O)R 21 , and -NH(=O)R 22 wherein each -(C 1～5 alkylene) independently represents 1 to 5 halide and / or 1 to 3 unsubstituted -(C 1～3 alkyl); Each R 8 are independently H, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 9 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 10 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 11 are independently H, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), 1 to 12 R 16 may be substituted with -(C 1～5 alkylene) p Carbocyclyl, 1 to 10 R 17 -heterocyclyl optionally substituted with, and 1 to 10 R 18 -heteroaryl optionally substituted with -(C 1～5 alkylene) is 1 to 5 halide and / or 1 to 3 unsubstituted -(C 1～3 alkyl); Each R 12 is 1 to 10 R 17 -heterocyclyl optionally substituted with; Each R 13 are independently H, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 14 are independently H, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), and -(C 1～5 alkylene) p OR 20 selected from the group consisting of: Each R 15 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Alternatively, two R attached to the same carbon atom 15 together to form a carbonyl group; Each R 16 are independently halides, -OMe, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 17 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 18 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 19 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 20 are independently H, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); Each R 21 are independently 1 to 10 R 17 -heterocyclyl, -N(R 11 ) 2 , and -OR 20 selected from the group consisting of: Each R 22 are independently unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), and -(C 1～5 alkylene) p OR 20 selected from the group consisting of: Each R 23 are independently unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), unsubstituted -(C 1～9 haloalkyl), and 1 to 12 R 24 -carbocyclyl, optionally substituted with; Each R 24 are independently halides, unsubstituted -(C 1～9 alkyl), unsubstituted -(C 2～9 alkenyl), unsubstituted -(C 2～9 alkynyl), and unsubstituted -(C 1～9 haloalkyl); each p is independently 0 or 1; Here, each H atom is independently 2 It may be replaced by H(D) (deuterium).

2. R 1 However, 1 to 10 R 3 may be substituted with 2. The compound of claim 1, selected from the group consisting of:

3. R 1 However, 1 to 3 R 3 may be substituted with 2. The compound of claim 1, selected from the group consisting of:

4. R 1 However, 1 to 3 R 3 may be substituted with 2. The compound of claim 1, selected from the group consisting of:

5. R 1 But non-substitution 2. The compound of claim 1, selected from the group consisting of:

6. R 3 is a halide, unsubstituted -(C 1～4 alkyl), unsubstituted -(C 1～4 haloalkyl), 1 to 3 R 9 -heterocyclyl optionally substituted with, and 1 to 3 R 10 2. The compound of claim 1, wherein the aryl group is selected from the group consisting of -carbocyclyl, optionally substituted with

7. R 2 is unsubstituted -(C 1～5 alkyl), unsubstituted -(C 1～5 haloalkyl), 1 to 3 R 5 may be substituted with -(C 1～2 alkylene) p Heterocyclyl and 1 to 3 R 7 may be substituted with -(C 1～2 alkylene) p carbocyclyl, wherein each -(C 1～5 2. The compound of claim 1, wherein each of the alkylene groups is independently optionally substituted with 1 to 2 halides.

8. The compound of formula I 5-(imidazo[1,2-a]pyridin-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine[1]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine[2]; N-(2-fluoro-2-methylpropyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[3]; N-(2,2-difluoropropyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[4]; 5-(Imidazo[1,2-a]pyridin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[5]; (R)-5-(imidazo[1,2-a]pyridin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[6]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[7]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[8]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[9]; (R)-5-(imidazo[1,2-a]pyridin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[10]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[11]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[12]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[13]; N-((1-fluorocyclobutyl)methyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[14]; N-((3-fluorooxetan-3-yl)methyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[15]; N-(cyclopropylmethyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[16]; (S)-N-(1-cyclopropylethyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[17]; (R)-N-(1-cyclopropylethyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[18]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[19]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[20]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[21]; N-cyclobutyl-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[22]; N-(3,3-difluorocyclobutyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[23]; N-(3,3-dimethylcyclobutyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[24]; 3-((5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [25]; 5-(Imidazo[1,2-a]pyridin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[26]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[27]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[28]; N-(cis-3-ethoxycyclobutyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[29]; N-(trans-3-ethoxycyclobutyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[30]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[31]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[32]; cis-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [33]; trans-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [34]; cis-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [35]; trans-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [36]; cis-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [37]; trans-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [38]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[39]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[40]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[41]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [42]; N-(4,4-difluorocyclohexyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[43]; cis-4-((5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [44]; (1s,4s)-4-((5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [45]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[46]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [47]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[48]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[49]; N-(cis-4-ethoxycyclohexyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[50]; N-(trans-4-ethoxycyclohexyl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[51]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[52]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [53]; cis-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [54]; trans-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [55]; cis-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [56]; trans-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [57]; cis-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [58]; trans-N 1 -(5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [59]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[60]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [61]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[62]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [63]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[64]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [65]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [66]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [67]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[68]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [69]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[70]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [71]; (6-(2-(isopropylamino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [72]; (6-(2-(isobutylamino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [73]; (6-(2-((2-fluoro-2-methylpropyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [74]; (6-(2-((2,2-difluoropropyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [75]; Pyrrolidin-1-yl(6-(2-((2,2,2-trifluoroethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)methanone [76]; (R)-Pyrrolidin-1-yl(6-(2-((1,1,1-trifluoropropan-2-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)methanone [77]; Pyrrolidin-1-yl(6-(2-((3,3,3-trifluoropropyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)methanone [78]; Pyrrolidin-1-yl(6-(2-((3,3,3-trifluoro-2,2-dimethylpropyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)methanone [79]; (6-(2-((2-methoxyethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [80]; (R)-(6-(2-((1-methoxypropan-2-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [81]; (6-(2-((2-isopropoxyethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [82]; (6-(2-(((1-methylcyclopropyl)methyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [83]; Pyrrolidin-1-yl(6-(2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)methanone [84]; (6-(2-(((1-fluorocyclobutyl)methyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [85]; (6-(2-(((3-fluorooxetan-3-yl)methyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [86]; (6-(2-((cyclopropylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [87]; (S)-(6-(2-((1-cyclopropylethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [88]; (R)-(6-(2-((1-cyclopropylethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [89]; (6-(2-((2-cyclopropyl-2,2-difluoroethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [90]; (6-(2-((oxetan-3-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [91]; Pyrrolidin-1-yl(6-(2-(((tetrahydrofuran-2-yl)methyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)methanone [92]; (6-(2-(cyclobutylamino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [93]; (6-(2-((3,3-difluorocyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [94]; (6-(2-((3,3-dimethylcyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [95]; (6-(2-((3-hydroxy-3-methylcyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [96]; (6-(2-((cis-3-methoxycyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [97]; (6-(2-((trans-3-methoxycyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [98]; (6-(2-((trans-3-(methoxymethyl)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [99]; (6-(2-((cis-3-ethoxycyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [100]; (6-(2-((trans-3-ethoxycyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [101]; (6-(2-((cis-3-(2-methoxyethoxy)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [102]; (6-(2-((trans-3-(2-methoxyethoxy)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [103]; (6-(2-((cis-3-aminocyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [104]; (6-(2-((trans-3-aminocyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [105]; (6-(2-((cis-3-(methylamino)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [106]; (6-(2-((trans-3-(methylamino)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [107]; (6-(2-((cis-3-(dimethylamino)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [108]; (6-(2-((trans-3-(dimethylamino)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [109]; (6-(2-((cis-3-morpholinocyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [110]; (6-(2-((trans-3-morpholinocyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [111]; (6-(2-((cis-3-(4-methylpiperazin-1-yl)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [112]; (6-(2-((trans-3-(4-methylpiperazin-1-yl)cyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [113]; (6-(2-((4,4-difluorocyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [114]; (6-(2-((cis-4-hydroxycyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [115]; (6-(2-(((1s,4s)-4-hydroxy-4-methylcyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [116]; (6-(2-((cis-4-methoxycyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [117]; (6-(2-((trans-4-methoxycyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [118]; (6-(2-((cis-4-(difluoromethoxy)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [119]; (6-(2-((trans-4-(difluoromethoxy)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [120]; (6-(2-((cis-4-ethoxycyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [121]; (6-(2-((trans-4-ethoxycyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [122]; (6-(2-((cis-4-(2-methoxyethoxy)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [123]; (6-(2-((trans-4-(2-methoxyethoxy)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [124]; (6-(2-((cis-4-aminocyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [125]; (6-(2-((trans-4-aminocyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [126]; (6-(2-((cis-4-(methylamino)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [127]; (6-(2-((trans-4-(methylamino)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [128]; (6-(2-((cis-4-(dimethylamino)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [129]; (6-(2-((trans-4-(dimethylamino)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [130]; (6-(2-((cis-4-morpholinocyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [131]; (6-(2-((trans-4-morpholinocyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [132]; (6-(2-((cis-4-(4-methylpiperazin-1-yl)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [133]; (6-(2-((trans-4-(4-methylpiperazin-1-yl)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [134]; (6-(2-((1-methylazetidin-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [135]; (6-(2-(oxetan-3-ylamino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [136]; (6-(2-((1-methylpiperidin-4-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [137]; Pyrrolidin-1-yl(6-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)methanone [138]; (6-(2-((6,6-difluorospiro[3.3]heptan-2-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [139]; (6-(2-((2-oxaspiro[3.3]heptan-6-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [140]; (6-(2-((2-methyl-2-azaspiro[3.3]heptan-6-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [141]; (6-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [142]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [143]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [144]; N-(2-fluoro-2-methylpropyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [145]; N-(2,2-difluoropropyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [146]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [147]; (R)-5-(imidazo[1,2-b]pyridazin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [148]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [149]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [150]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [151]; (R)-5-(imidazo[1,2-b]pyridazin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [152]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [153]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [154]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [155]; N-((1-fluorocyclobutyl)methyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [156]; N-((3-fluorooxetan-3-yl)methyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [157]; N-(cyclopropylmethyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [158]; (S)-N-(1-cyclopropylethyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [159]; (R)-N-(1-cyclopropylethyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [160]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [161]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [162]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [163]; N-cyclobutyl-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [164]; N-(3,3-difluorocyclobutyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [165]; N-(3,3-dimethylcyclobutyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [166]; 3-((5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [167]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [168]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [169]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [170]; N-(cis-3-ethoxycyclobutyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [171]; N-(trans-3-ethoxycyclobutyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [172]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [173]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [174]; cis-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [175]; trans-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [176]; cis-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [177]; trans-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [178]; cis-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [179]; trans-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [180]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [181]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [182]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [183]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [184]; N-(4,4-difluorocyclohexyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [185]; cis-4-((5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [186]; (1s,4s)-4-((5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [187]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [188]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [189]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[190]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[191]; N-(cis-4-ethoxycyclohexyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[192]; N-(trans-4-ethoxycyclohexyl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [193]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [194]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [195]; cis-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [196]; trans-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [197]; cis-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [198]; trans-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [199]; cis-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [200]; trans-N 1 -(5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [201]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[202]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[203]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[204]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[205]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[206]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[207]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[208]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[209]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[210]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[211]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[212]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [213]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [214]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine[215]; N-(2-fluoro-2-methylpropyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[216]; N-(2,2-difluoropropyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[217]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [218]; (R)-5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[219]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[220]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[221]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[222]; (R)-5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [223]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [224]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[225]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[226]; N-((1-fluorocyclobutyl)methyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[227]; N-((3-fluorooxetan-3-yl)methyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [228]; N-(cyclopropylmethyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[229]; (S)-N-(1-cyclopropylethyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[230]; (R)-N-(1-cyclopropylethyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [231]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[232]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [233]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [234]; N-cyclobutyl-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [235]; N-(3,3-difluorocyclobutyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [236]; N-(3,3-dimethylcyclobutyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [237]; 3-((5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [238]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [239]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [240]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [241]; N-(cis-3-ethoxycyclobutyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [242]; N-(trans-3-ethoxycyclobutyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [243]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [244]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [245]; cis-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [246]; trans-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [247]; cis-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [248]; trans-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [249]; cis-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [250]; trans-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [251]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [252]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [253]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [254]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[255]; N-(4,4-difluorocyclohexyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[256]; cis-4-((5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [257]; (1s,4s)-4-((5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [258]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[259]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[260]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[261]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[262]; N-(cis-4-ethoxycyclohexyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[263]; N-(trans-4-ethoxycyclohexyl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[264]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[265]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [266]; cis-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [267]; trans-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [268]; cis-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [269]; trans-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [270]; cis-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [271]; trans-N 1 -(5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [272]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [273]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [274]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[275]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [276]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[277]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [278]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [279]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [280]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [281]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [282]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [283]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [284]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [285]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [286]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [287]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2,2-difluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [288]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [289]; (R)-5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [290]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [291]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [292]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [293]; (R)-5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [294]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [295]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [296]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [297]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-((1-fluorocyclobutyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [298]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [299]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cyclopropylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[300]; (S)-5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(1-cyclopropylethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [301]; (R)-5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(1-cyclopropylethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [302]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-cyclopropyl-2,2-difluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [303]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [304]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [305]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-cyclobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [306]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(3,3-difluorocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [307]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(3,3-dimethylcyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [308]; 3-((5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [309]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [310]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [311]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [312]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-ethoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [313]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-ethoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [314]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [315]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [316]; cis-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [317]; trans-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [318]; cis-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [319]; trans-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [320]; cis-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [321]; trans-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [322]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [323]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [324]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [325]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [326]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(4,4-difluorocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [327]; cis-4-((5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [328]; (1s,4s)-4-((5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [329]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [330]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [331]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(difluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [332]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(difluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [333]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-ethoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [334]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-ethoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [335]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [336]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [337]; cis-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [338]; trans-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [339]; cis-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [340]; trans-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [341]; cis-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [342]; trans-N 1 -(5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [343]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [344]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [345]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [346]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [347]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [348]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [349]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [350]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [351]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(6,6-difluorospiro[3.3]heptan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [352]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [353]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [354]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [355]; N-Isopropyl-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [356]; N-isobutyl-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [357]; N-(2-fluoro-2-methylpropyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [358]; N-(2,2-difluoropropyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [359]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [360]; (R)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [361]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [362]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [363]; N-(2-methoxyethyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [364]; (R)-N-(1-methoxypropan-2-yl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [365]; N-(2-isopropoxyethyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[366]; N-((1-methylcyclopropyl)methyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [367]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [368]; N-((1-fluorocyclobutyl)methyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [369]; N-((3-fluorooxetan-3-yl)methyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [370]; N-(cyclopropylmethyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [371]; (S)-N-(1-cyclopropylethyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [372]; (R)-N-(1-cyclopropylethyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [373]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [374]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [375]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [376]; N-cyclobutyl-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [377]; N-(3,3-difluorocyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [378]; N-(3,3-dimethylcyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [379]; 1-Methyl-3-((5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [380]; N-(cis-3-Methoxycyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [381]; N-(trans-3-methoxycyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [382]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [383]; N-(cis-3-ethoxycyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [384]; N-(trans-3-ethoxycyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [385]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [386]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [387]; cis-N 1 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [388]; trans-N 1 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [389]; cis-N 1 -methyl-N 3 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [390]; trans-N 1 -methyl-N 3 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [391]; cis-N 1 ,N 1 -Dimethyl-N 3 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [392]; trans-N 1 ,N 1 -Dimethyl-N 3 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [393]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [394]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [395]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [396]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [397]; N-(4,4-difluorocyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [398]; cis-4-((5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [399]; (1s,4s)-1-methyl-4-((5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [400]; N-(cis-4-Methoxycyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[401]; N-(trans-4-Methoxycyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [402]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [403]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [404]; N-(cis-4-ethoxycyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[405]; N-(trans-4-ethoxycyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [406]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[407]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [408]; cis-N 1 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [409]; trans-N 1 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [410]; cis-N 1 -methyl-N 4 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [411]; trans-N 1 -methyl-N 4 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [412]; cis-N 1 ,N 1 -Dimethyl-N 4 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [413]; trans-N 1 ,N 1 -Dimethyl-N 4 -(5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [414]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [415]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [416]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [417]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [418]; N-(1-methylazetidin-3-yl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[419]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[420]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [421]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [422]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[423]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [424]; N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[425]; N-(1-methyl-1H-pyrazol-4-yl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [426]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [427]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [428]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [429]; N-(2,2-difluoropropyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [430]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [431]; (R)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [432]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [433]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [434]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [435]; (R)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [436]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [437]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [438]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [439]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-((1-fluorocyclobutyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [440]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [441]; N-(cyclopropylmethyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [442]; (S)-N-(1-cyclopropylethyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [443]; (R)-N-(1-cyclopropylethyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [444]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [445]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [446]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [447]; N-cyclobutyl-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [448]; N-(3,3-difluorocyclobutyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [449]; N-(3,3-dimethylcyclobutyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[450]; 3-((5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [451]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [452]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [453]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [454]; N-(cis-3-ethoxycyclobutyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [455]; N-(trans-3-ethoxycyclobutyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [456]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [457]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [458]; cis-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [459]; trans-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [460]; cis-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [461]; trans-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [462]; cis-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [463]; trans-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [464]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [465]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [466]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [467]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [468]; N-(4,4-difluorocyclohexyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [469]; cis-4-((5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [470]; (1s,4s)-4-((5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [471]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [472]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [473]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [474]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [475]; N-(cis-4-ethoxycyclohexyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [476]; N-(trans-4-ethoxycyclohexyl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [477]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [478]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [479]; cis-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [480]; trans-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [481]; cis-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [482]; trans-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [483]; cis-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [484]; trans-N 1 -(5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [485]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [486]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [487]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [488]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [489]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [490]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [491]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [492]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [493]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [494]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [495]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [496]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [497]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [498]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [499]; and 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[500] 2. The compound of claim 1, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

9. The compound of formula I N-(2,2-difluoropropyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [501]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [502]; (R)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [503]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [504]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [505]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [506]; (R)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [507]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [508]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [509]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [510]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-((1-fluorocyclobutyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [511]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [512]; N-(cyclopropylmethyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [513]; (S)-N-(1-cyclopropylethyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [514]; (R)-N-(1-cyclopropylethyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [515]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [516]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [517]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [518]; N-cyclobutyl-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [519]; N-(3,3-difluorocyclobutyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [520]; N-(3,3-dimethylcyclobutyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [521]; 3-((5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [522]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [523]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [524]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [525]; N-(cis-3-ethoxycyclobutyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [526]; N-(trans-3-ethoxycyclobutyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [527]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [528]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [529]; cis-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [530]; trans-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [531]; cis-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [532]; trans-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -methylcyclobutane-1,3-diamine [533]; cis-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [534]; trans-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [535]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [536]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [537]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [538]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [539]; N-(4,4-difluorocyclohexyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [540]; cis-4-((5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [541]; (1s,4s)-4-((5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [542]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [543]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [544]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [545]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [546]; N-(cis-4-ethoxycyclohexyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [547]; N-(trans-4-ethoxycyclohexyl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [548]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [549]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [550]; cis-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [551]; trans-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [552]; cis-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [553]; trans-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [554]; cis-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [555]; trans-N 1 -(5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [556]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [557]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [558]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [559]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [560]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [561]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [562]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [563]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [564]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [565]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [566]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [567]; 5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [568]; N-Isopropyl-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [569]; N-Isobutyl-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [570]; N-(2-fluoro-2-methylpropyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [571]; N-(2,2-difluoropropyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [572]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [573]; (R)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [574]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [575]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [576]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [577]; (R)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [578]; N-(2-isopropoxyethyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [579]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [580]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [581]; N-((1-fluorocyclobutyl)methyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [582]; N-((3-fluorooxetan-3-yl)methyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [583]; N-(cyclopropylmethyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [584]; (S)-N-(1-cyclopropylethyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [585]; (R)-N-(1-cyclopropylethyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [586]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [587]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [588]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [589]; N-cyclobutyl-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [590]; N-(3,3-difluorocyclobutyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [591]; N-(3,3-dimethylcyclobutyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [592]; 3-((5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [593]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [594]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [595]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [596]; N-(cis-3-ethoxycyclobutyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [597]; N-(trans-3-ethoxycyclobutyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [598]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [599]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[600]; cis-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [601]; trans-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [602]; cis-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [603]; trans-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [604]; cis-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [605]; trans-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [606]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [607]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [608]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [609]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[610]; N-(4,4-difluorocyclohexyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[611]; cis-4-((5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [612]; (1s,4s)-4-((5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [613]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [614]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [615]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[616]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[617]; N-(cis-4-ethoxycyclohexyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[618]; N-(trans-4-ethoxycyclohexyl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[619]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[620]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [621]; cis-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [622]; trans-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [623]; cis-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [624]; trans-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [625]; cis-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [626]; trans-N 1 -(5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [627]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [628]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [629]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [630]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [631]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [632]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [633]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [634]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [635]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [636]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [637]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [638]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [639]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [640]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [641]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [642]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2,2-difluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [643]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [644]; (R)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [645]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [646]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [647]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [648]; (R)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [649]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[650]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [651]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [652]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-fluorocyclobutyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [653]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [654]; N-(cyclopropylmethyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [655]; (S)-N-(1-cyclopropylethyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [656]; (R)-N-(1-cyclopropylethyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [657]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [658]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [659]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [660]; N-cyclobutyl-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [661]; N-(3,3-difluorocyclobutyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [662]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3-dimethylcyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [663]; 3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [664]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [665]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [666]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [667]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-ethoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [668]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-ethoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [669]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [670]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [671]; cis-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [672]; trans-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [673]; cis-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [674]; trans-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [675]; cis-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [676]; trans-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [677]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [678]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [679]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [680]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [681]; N-(4,4-difluorocyclohexyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [682]; cis-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [683]; (1s,4s)-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [684]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [685]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [686]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(difluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [687]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(difluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [688]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-ethoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [689]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-ethoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [690]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [691]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [692]; cis-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [693]; trans-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [694]; cis-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [695]; trans-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [696]; cis-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [697]; trans-N 1 -(5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [698]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [699]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[700]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [701]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [702]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [703]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [704]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [705]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [706]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(6,6-difluorospiro[3.3]heptan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [707]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [708]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [709]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [710]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [711]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [712]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [713]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2,2-difluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [714]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [715]; (R)-5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [716]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [717]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [718]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [719]; (R)-5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [720]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [721]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [722]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [723]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-fluorocyclobutyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [724]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [725]; N-(cyclopropylmethyl)-5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [726]; (S)-N-(1-cyclopropylethyl)-5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [727]; (R)-N-(1-cyclopropylethyl)-5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [728]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [729]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [730]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [731]; N-cyclobutyl-5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [732]; N-(3,3-difluorocyclobutyl)-5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [733]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3-dimethylcyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [734]; 3-((5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [735]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [736]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [737]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [738]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-ethoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [739]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-ethoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [740]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [741]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [742]; cis-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [743]; trans-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [744]; cis-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [745]; trans-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [746]; cis-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [747]; trans-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [748]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [749]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[750]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [751]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [752]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(4,4-difluorocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [753]; cis-4-((5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [754]; (1s,4s)-4-((5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [755]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [756]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [757]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(difluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [758]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(difluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [759]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-ethoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [760]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-ethoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [761]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [762]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [763]; cis-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [764]; trans-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [765]; cis-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [766]; trans-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [767]; cis-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [768]; trans-N 1 -(5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [769]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [770]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [771]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [772]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [773]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [774]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [775]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [776]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [777]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(6,6-difluorospiro[3.3]heptan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [778]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [779]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [780]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [781]; N-Isopropyl-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [782]; N-isobutyl-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [783]; N-(2-fluoro-2-methylpropyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [784]; N-(2,2-difluoropropyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [785]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [786]; (R)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [787]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [788]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [789]; N-(2-Methoxyethyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [790]; (R)-N-(1-methoxypropan-2-yl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [791]; N-(2-isopropoxyethyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [792]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [793]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [794]; N-((1-fluorocyclobutyl)methyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [795]; N-((3-fluorooxetan-3-yl)methyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [796]; N-(cyclopropylmethyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [797]; (S)-N-(1-cyclopropylethyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [798]; (R)-N-(1-cyclopropylethyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [799]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[800]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [801]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [802]; N-cyclobutyl-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [803]; N-(3,3-difluorocyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [804]; N-(3,3-dimethylcyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [805]; 1-methyl-3-((5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [806]; N-(cis-3-Methoxycyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [807]; N-(trans-3-methoxycyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [808]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [809]; N-(cis-3-ethoxycyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [810]; N-(trans-3-ethoxycyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [811]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [812]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [813]; cis-N 1 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [814]; trans-N 1 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [815]; cis-N 1 -methyl-N 3 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [816]; trans-N 1 -methyl-N 3 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [817]; cis-N 1 ,N 1 -Dimethyl-N 3 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [818]; trans-N 1 ,N 1 -Dimethyl-N 3 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [819]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [820]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [821]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [822]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [823]; N-(4,4-difluorocyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [824]; cis-4-((5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [825]; (1s,4s)-1-methyl-4-((5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [826]; N-(cis-4-Methoxycyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [827]; N-(trans-4-Methoxycyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [828]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [829]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [830]; N-(cis-4-ethoxycyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [831]; N-(trans-4-ethoxycyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [832]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [833]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [834]; cis-N 1 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [835]; trans-N 1 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [836]; cis-N 1 -methyl-N 4 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [837]; trans-N 1 -methyl-N 4 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [838]; cis-N 1 ,N 1 -Dimethyl-N 4 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [839]; trans-N 1 ,N 1 -Dimethyl-N 4 -(5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [840]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [841]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [842]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [843]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [844]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [845]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [846]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [847]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [848]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [849]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [850]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [851]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [852]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [853]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [854]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [855]; N-(2,2-difluoropropyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [856]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [857]; (R)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [858]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [859]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [860]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [861]; (R)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [862]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [863]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [864]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [865]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-fluorocyclobutyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [866]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [867]; N-(cyclopropylmethyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [868]; (S)-N-(1-cyclopropylethyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [869]; (R)-N-(1-cyclopropylethyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [870]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [871]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [872]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [873]; N-cyclobutyl-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [874]; N-(3,3-difluorocyclobutyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [875]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3-dimethylcyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [876]; 3-((5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [877]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [878]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [879]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [880]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-ethoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [881]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-ethoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [882]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [883]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [884]; cis-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [885]; trans-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [886]; cis-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [887]; trans-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [888]; cis-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -dimethylcyclobutane-1,3-diamine [889]; trans-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [890]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [891]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [892]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [893]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [894]; N-(4,4-difluorocyclohexyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [895]; cis-4-((5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [896]; (1s,4s)-4-((5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [897]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [898]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [899]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[900]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [901]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-ethoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [902]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-ethoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [903]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [904]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [905]; cis-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [906]; trans-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [907]; cis-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [908]; trans-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [909]; cis-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [910]; trans-N 1 -(5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -dimethylcyclohexane-1,4-diamine [911]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [912]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [913]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [914]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [915]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [916]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [917]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [918]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [919]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[920]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [921]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [922]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [923]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [924]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [925]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-fluoro-2-methylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [926]; N-(2,2-difluoropropyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [927]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [928]; (R)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [929]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [930]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [931]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [932]; (R)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [933]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [934]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [935]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [936]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-fluorocyclobutyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [937]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [938]; N-(cyclopropylmethyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [939]; (S)-N-(1-cyclopropylethyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [940]; (R)-N-(1-cyclopropylethyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [941]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [942]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [943]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [944]; N-cyclobutyl-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [945]; N-(3,3-difluorocyclobutyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [946]; N-(3,3-dimethylcyclobutyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [947]; 3-((5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [948]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [949]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [950]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [951]; N-(cis-3-ethoxycyclobutyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [952]; N-(trans-3-ethoxycyclobutyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [953]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [954]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [955]; cis-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [956]; trans-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [957]; cis-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [958]; trans-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [959]; cis-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [960]; trans-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [961]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [962]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [963]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [964]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [965]; N-(4,4-difluorocyclohexyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [966]; cis-4-((5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [967]; (1s,4s)-4-((5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [968]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [969]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [970]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [971]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [972]; N-(cis-4-ethoxycyclohexyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [973]; N-(trans-4-ethoxycyclohexyl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [974]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [975]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [976]; cis-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [977]; trans-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [978]; cis-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -methylcyclohexane-1,4-diamine [979]; trans-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [980]; cis-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [981]; trans-N 1 -(5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [982]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [983]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [984]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [985]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [986]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [987]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [988]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [989]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [990]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [991]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [992]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [993]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [994]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [995]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [996]; N-(2-fluoro-2-methylpropyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [997]; N-(2,2-difluoropropyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [998]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [999]; and (R)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1000] 2. The compound of claim 1, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

10. The compound of formula I 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1001]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1002]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1003]; (R)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1004]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1005]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1006]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1007]; N-((1-fluorocyclobutyl)methyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1008]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1009]; N-(cyclopropylmethyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1010]; (S)-N-(1-cyclopropylethyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1011]; (R)-N-(1-cyclopropylethyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1012]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1013]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1014]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1015]; N-cyclobutyl-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1016]; N-(3,3-difluorocyclobutyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1017]; N-(3,3-dimethylcyclobutyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1018]; 3-((5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1019]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1020]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1021]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1022]; N-(cis-3-ethoxycyclobutyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1023]; N-(trans-3-ethoxycyclobutyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1024]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1025]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1026]; cis-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1027]; trans-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1028]; cis-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1029]; trans-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1030]; cis-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1031]; trans-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1032]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1033]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1034]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1035]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1036]; N-(4,4-difluorocyclohexyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1037]; cis-4-((5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1038]; (1s,4s)-4-((5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1039]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1040]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1041]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1042]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1043]; N-(cis-4-ethoxycyclohexyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1044]; N-(trans-4-ethoxycyclohexyl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1045]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1046]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1047]; cis-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1048]; trans-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1049]; cis-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1050]; trans-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1051]; cis-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1052]; trans-N 1 -(5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1053]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1054]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1055]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1056]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1057]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1058]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1059]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1060]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1061]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1062]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1063]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1064]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1065]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-isopropylpyrrolo[2,1-f][1,2,4]triazin-2-amine [1066]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-isobutylpyrrolo[2,1-f][1,2,4]triazin-2-amine [1067]; N-(2-fluoro-2-methylpropyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1068]; N-(2,2-difluoropropyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1069]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1070]; (R)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1071]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1072]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1073]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1074]; (R)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1075]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-isopropoxyethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1076]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1077]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1078]; N-((1-fluorocyclobutyl)methyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1079]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3-fluorooxetan-3-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1080]; N-(cyclopropylmethyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1081]; (S)-N-(1-cyclopropylethyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1082]; (R)-N-(1-cyclopropylethyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1083]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1084]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1085]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1086]; N-cyclobutyl-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1087]; N-(3,3-difluorocyclobutyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1088]; N-(3,3-dimethylcyclobutyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1089]; 3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1090]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1091]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-methoxycyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1092]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1093]; N-(cis-3-ethoxycyclobutyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1094]; N-(trans-3-ethoxycyclobutyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1095]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1096]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(2-methoxyethoxy)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1097]; cis-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1098]; trans-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1099]; cis-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1100]; trans-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1101]; cis-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1102]; trans-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1103]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1104]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1105]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1106]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1107]; N-(4,4-difluorocyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1108]; cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1109]; (1s,4s)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol[1110]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1111]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-methoxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1112]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1113]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1114]; N-(cis-4-ethoxycyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1115]; N-(trans-4-ethoxycyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1116]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1117]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(2-methoxyethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1118]; cis-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1119]; trans-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1120]; cis-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1121]; trans-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1122]; cis-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1123]; trans-N 1 -(5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1124]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1125]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1126]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1127]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1128]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1129]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1130]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1131]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1132]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1133]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1134]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1135]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1136]; N-Isopropyl-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1137]; N-isobutyl-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1138]; N-(2-fluoro-2-methylpropyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1139]; N-(2,2-difluoropropyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1140]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1141]; (R)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1142]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1143]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1144]; N-(2-methoxyethyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1145]; (R)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methoxypropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1146]; N-(2-isopropoxyethyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1147]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1148]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1149]; N-((1-fluorocyclobutyl)methyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1150]; N-((3-fluorooxetan-3-yl)methyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1151]; N-(cyclopropylmethyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1152]; (S)-N-(1-cyclopropylethyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1153]; (R)-N-(1-cyclopropylethyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1154]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1155]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1156]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1157]; N-cyclobutyl-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1158]; N-(3,3-difluorocyclobutyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1159]; N-(3,3-dimethylcyclobutyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1160]; 3-((5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1161]; N-(cis-3-methoxycyclobutyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1162]; N-(trans-3-methoxycyclobutyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1163]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(methoxymethyl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1164]; N-(cis-3-ethoxycyclobutyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1165]; N-(trans-3-ethoxycyclobutyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1166]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1167]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1168]; cis-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1169]; trans-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1170]; cis-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1171]; trans-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1172]; cis-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1173]; trans-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1174]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1175]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1176]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1177]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1178]; N-(4,4-difluorocyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1179]; cis-4-((5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1180]; (1s,4s)-4-((5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1181]; N-(cis-4-Methoxycyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1182]; N-(trans-4-Methoxycyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1183]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1184]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1185]; N-(cis-4-ethoxycyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1186]; N-(trans-4-ethoxycyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1187]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1188]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1189]; cis-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1190]; trans-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1191]; cis-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1192]; trans-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1193]; cis-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1194]; trans-N 1 -(5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1195]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1196]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1197]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1198]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1199]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1200]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1201]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1202]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1203]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1204]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1205]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1206]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1207]; N-isopropyl-5-(1-methyl-1H-benzo[a]pyridyl] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1208]; N-isobutyl-5-(1-methyl-1H-benzo[a]thiazolinone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1209]; N-(2-fluoro-2-methylpropyl)-5-(1-methyl-1H-benzo[b] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1210]; N-(2,2-difluoropropyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-1-yl)-benzo[b]pyridin-1-yl ... [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1211]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1212]; (R)-5-(1-methyl-1H-benzo[a]pyridin-1-yl] [d][1,2,3]triazol-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1213]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1214]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1215]; N-(2-methoxyethyl)-5-(1-methyl-1H-benzo[a]methyl]- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1216]; (R)-N-(1-methoxypropan-2-yl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1217]; N-(2-isopropoxyethyl)-5-(1-methyl-1H-benzo[a]methyl]- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1218]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1219]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1220]; N-((1-fluorocyclobutyl)methyl)-5-(1-methyl-1H-benzo[a]methyl]- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1221]; N-((3-fluorooxetan-3-yl)methyl)-5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1222]; N-(cyclopropylmethyl)-5-(1-methyl-1H-benzo[a]methyl]- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1223]; (S)-N-(1-cyclopropylethyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-1-yl)- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1224]; (R)-N-(1-cyclopropylethyl)-5-(1-methyl-1H-benzo[a]pyridin-1-yl]-4-methyl-2-(2-methyl-1H-benzo[a]pyridin-1-yl) ... [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1225]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(1-methyl-1H-benzo[a]methyl]- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1226]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1227]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1228]; N-cyclobutyl-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-1-yl) [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1229]; N-(3,3-difluorocyclobutyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-1-yl)- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1230]; N-(3,3-dimethylcyclobutyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-1-one [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1231]; 1-methyl-3-((5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1232]; N-(cis-3-methoxycyclobutyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-1-yl)- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1233]; N-(trans-3-methoxycyclobutyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-1-yl)- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1234]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-4-one [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1235]; N-(cis-3-ethoxycyclobutyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-1-yl)- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1236]; N-(trans-3-ethoxycyclobutyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-4-yl)-2-methyl-1H-benzo[b]pyridin-2-yl]pyridin-4-yl [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1237]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(1-methyl-1H-benzo[a]pyridin-2-yl]pyridin-2-yl)- [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1238]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(1-methyl-1H-benzo[a]pyridyl] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1239]; cis-N 1 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1240]; trans-N 1 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1241]; cis-N 1 -methyl-N 3 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1242]; trans-N 1 -methyl-N 3 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1243]; cis-N 1 ,N 1 -Dimethyl-N 3 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1244]; trans-N 1 ,N 1 -Dimethyl-N 3 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1245]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1246]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1247]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1248]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1249]; N-(4,4-difluorocyclohexyl)-5-(1-methyl-1H-benzo[a]pyrrolidone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1250]; cis-4-((5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1251]; (1s,4s)-1-methyl-4-((5-(1-methyl-1H-benzo) [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1252]; N-(cis-4-methoxycyclohexyl)-5-(1-methyl-1H-benzo[a]pyrrolidone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1253]; N-(trans-4-methoxycyclohexyl)-5-(1-methyl-1H-benzo[a]pyrrolidone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1254]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(1-methyl-1H-benzo[a]pyrrolidone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1255]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(1-methyl-1H-benzo[a]pyrrolidone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1256]; N-(cis-4-ethoxycyclohexyl)-5-(1-methyl-1H-benzo[a]pyrrolidone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1257]; N-(trans-4-ethoxycyclohexyl)-5-(1-methyl-1H-benzo[a]pyrrolidone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1258]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(1-methyl-1H-benzo[a]thiazolinone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1259]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(1-methyl-1H-benzo[a]thiazolinone] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1260]; cis-N 1 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1261]; trans-N 1 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1262]; cis-N 1 -methyl-N 4 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1263]; trans-N 1 -methyl-N 4 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1264]; cis-N 1 ,N 1 -Dimethyl-N 4 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1265]; trans-N 1 ,N 1 -Dimethyl-N 4 -(5-(1-methyl-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1266]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1267]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1268]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1269]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1270]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1271]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1272]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1273]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1274]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(1-methyl-1H-benzo) [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1275]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1276]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1277]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1278]; N-Isopropyl-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1279]; N-isobutyl-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1280]; N-(2-fluoro-2-methylpropyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1281]; N-(2,2-difluoropropyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1282]; 5-(Quinolin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1283]; (R)-5-(quinolin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1284]; 5-(Quinolin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1285]; 5-(quinolin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1286]; N-(2-Methoxyethyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1287]; (R)-N-(1-methoxypropan-2-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1288]; N-(2-isopropoxyethyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1289]; N-((1-methylcyclopropyl)methyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1290]; 5-(Quinolin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1291]; N-((1-fluorocyclobutyl)methyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1292]; N-((3-fluorooxetan-3-yl)methyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1293]; N-(cyclopropylmethyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1294]; (S)-N-(1-cyclopropylethyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1295]; (R)-N-(1-cyclopropylethyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1296]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1297]; N-(oxetan-3-ylmethyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1298]; 5-(quinolin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1299]; N-cyclobutyl-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1300]; N-(3,3-difluorocyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1301]; N-(3,3-dimethylcyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1302]; 1-methyl-3-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1303]; N-(cis-3-Methoxycyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1304]; N-(trans-3-methoxycyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1305]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1306]; N-(cis-3-ethoxycyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1307]; N-(trans-3-ethoxycyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1308]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1309]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1310]; cis-N 1 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1311]; trans-N 1 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1312]; cis-N 1 -methyl-N 3 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1313]; trans-N 1 -methyl-N 3 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1314]; cis-N 1 ,N 1 -Dimethyl-N 3 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1315]; trans-N 1 ,N 1 -Dimethyl-N 3 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1316]; N-(cis-3-morpholinocyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1317]; N-(trans-3-morpholinocyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1318]; N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1319]; N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1320]; N-(4,4-difluorocyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1321]; cis-4-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1322]; (1s,4s)-1-methyl-4-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1323]; N-(cis-4-Methoxycyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1324]; N-(trans-4-Methoxycyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1325]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1326]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1327]; N-(cis-4-ethoxycyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1328]; N-(trans-4-ethoxycyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1329]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1330]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1331]; cis-N 1 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1332]; trans-N 1 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1333]; cis-N 1 -methyl-N 4 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1334]; trans-N 1 -methyl-N 4 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1335]; cis-N 1 ,N 1 -Dimethyl-N 4 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1336]; trans-N 1 ,N 1 -Dimethyl-N 4 -(5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1337]; N-(cis-4-morpholinocyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1338]; N-(trans-4-morpholinocyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1339]; N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1340]; N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1341]; N-(1-methylazetidin-3-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1342]; N-(oxetan-3-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1343]; N-(1-methylpiperidin-4-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1344]; 5-(quinolin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1345]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1346]; 5-(quinolin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1347]; N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1348]; N-(1-methyl-1H-pyrazol-4-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1349]; N-Isopropyl-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1350]; N-isobutyl-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1351]; N-(2-fluoro-2-methylpropyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1352]; N-(2,2-difluoropropyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1353]; 5-(quinoxalin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1354]; (R)-5-(quinoxalin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1355]; 5-(quinoxalin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1356]; 5-(quinoxalin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1357]; N-(2-Methoxyethyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1358]; (R)-N-(1-methoxypropan-2-yl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1359]; N-(2-isopropoxyethyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1360]; N-((1-methylcyclopropyl)methyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1361]; 5-(quinoxalin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1362]; N-((1-fluorocyclobutyl)methyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1363]; N-((3-fluorooxetan-3-yl)methyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1364]; N-(cyclopropylmethyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1365]; (S)-N-(1-cyclopropylethyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1366]; (R)-N-(1-cyclopropylethyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1367]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1368]; N-(oxetan-3-ylmethyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1369]; 5-(quinoxalin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1370]; N-cyclobutyl-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1371]; N-(3,3-difluorocyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1372]; N-(3,3-dimethylcyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1373]; 1-methyl-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1374]; N-(cis-3-Methoxycyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1375]; N-(trans-3-Methoxycyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1376]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1377]; N-(cis-3-ethoxycyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1378]; N-(trans-3-ethoxycyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1379]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1380]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1381]; cis-N 1 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1382]; trans-N 1 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1383]; cis-N 1 -methyl-N 3 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1384]; trans-N 1 -methyl-N 3 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1385]; cis-N 1 ,N 1 -Dimethyl-N 3 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1386]; trans-N 1 ,N 1 -Dimethyl-N 3 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1387]; N-(cis-3-morpholinocyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1388]; N-(trans-3-morpholinocyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1389]; N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1390]; N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1391]; N-(4,4-difluorocyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1392]; cis-4-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1393]; (1s,4s)-1-methyl-4-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1394]; N-(cis-4-Methoxycyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1395]; N-(trans-4-Methoxycyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1396]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1397]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1398]; N-(cis-4-ethoxycyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1399]; N-(trans-4-ethoxycyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1400]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1401]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1402]; cis-N 1 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1403]; trans-N 1 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1404]; cis-N 1 -methyl-N 4 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1405]; trans-N 1 -methyl-N 4 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1406]; cis-N 1 ,N 1 -Dimethyl-N 4 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1407]; trans-N 1 ,N 1 -Dimethyl-N 4 -(5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1408]; N-(cis-4-morpholinocyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1409]; N-(trans-4-morpholinocyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1410]; N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1411]; N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1412]; N-(1-methylazetidin-3-yl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1413]; N-(oxetan-3-yl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1414]; N-(1-methylpiperidin-4-yl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1415]; 5-(quinoxalin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1416]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1417]; 5-(quinoxalin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1418]; N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1419]; N-(1-methyl-1H-pyrazol-4-yl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1420]; N-Isopropyl-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1421]; N-isobutyl-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1422]; N-(2-fluoro-2-methylpropyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1423]; N-(2,2-difluoropropyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1424]; 5-(4-Methoxyquinazolin-6-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1425]; (R)-5-(4-methoxyquinazolin-6-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1426]; 5-(4-Methoxyquinazolin-6-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1427]; 5-(4-Methoxyquinazolin-6-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1428]; N-(2-Methoxyethyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1429]; (R)-N-(1-methoxypropan-2-yl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1430]; N-(2-isopropoxyethyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1431]; 5-(4-Methoxyquinazolin-6-yl)-N-((1-methylcyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1432]; 5-(4-Methoxyquinazolin-6-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1433]; N-((1-fluorocyclobutyl)methyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1434]; N-((3-fluorooxetan-3-yl)methyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1435]; N-(cyclopropylmethyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1436]; (S)-N-(1-cyclopropylethyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1437]; (R)-N-(1-cyclopropylethyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1438]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1439]; 5-(4-Methoxyquinazolin-6-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1440]; 5-(4-Methoxyquinazolin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1441]; N-cyclobutyl-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1442]; N-(3,3-difluorocyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1443]; N-(3,3-dimethylcyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1444]; 3-((5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1445]; N-(cis-3-methoxycyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1446]; N-(trans-3-methoxycyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1447]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1448]; N-(cis-3-ethoxycyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1449]; N-(trans-3-ethoxycyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1450]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1451]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1452]; cis-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1453]; trans-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1454]; cis-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1455]; trans-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1456]; cis-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1457]; trans-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1458]; 5-(4-Methoxyquinazolin-6-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1459]; 5-(4-Methoxyquinazolin-6-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1460]; 5-(4-Methoxyquinazolin-6-yl)-N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1461]; 5-(4-Methoxyquinazolin-6-yl)-N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1462]; N-(4,4-difluorocyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1463]; cis-4-((5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1464]; (1s,4s)-4-((5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1465]; N-(cis-4-Methoxycyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1466]; N-(trans-4-Methoxycyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1467]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1468]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1469]; N-(cis-4-ethoxycyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1470]; N-(trans-4-ethoxycyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1471]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1472]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1473]; cis-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1474]; trans-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1475]; cis-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1476]; trans-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1477]; cis-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1478]; trans-N 1 -(5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1479]; 5-(4-Methoxyquinazolin-6-yl)-N-(cis-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1480]; 5-(4-Methoxyquinazolin-6-yl)-N-(trans-4-morpholinocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1481]; 5-(4-Methoxyquinazolin-6-yl)-N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1482]; 5-(4-Methoxyquinazolin-6-yl)-N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1483]; 5-(4-Methoxyquinazolin-6-yl)-N-(1-methylazetidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1484]; 5-(4-Methoxyquinazolin-6-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1485]; 5-(4-Methoxyquinazolin-6-yl)-N-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1486]; 5-(4-Methoxyquinazolin-6-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1487]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1488]; 5-(4-Methoxyquinazolin-6-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1489]; 5-(4-Methoxyquinazolin-6-yl)-N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1490]; 5-(4-Methoxyquinazolin-6-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1491]; N-Isopropyl-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1492]; N-isobutyl-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1493]; N-(2-fluoro-2-methylpropyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1494]; N-(2,2-difluoropropyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1495]; 5-(1,8-naphthyridin-3-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1496]; (R)-5-(1,8-naphthyridin-3-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1497]; 5-(1,8-naphthyridin-3-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1498]; 5-(1,8-naphthyridin-3-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1499]; and N-(2-Methoxyethyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1500] 2. The compound of claim 1, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

11. The compound of formula I (R)-N-(1-methoxypropan-2-yl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1501]; N-(2-isopropoxyethyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1502]; N-((1-methylcyclopropyl)methyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1503]; 5-(1,8-naphthyridin-3-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1504]; N-((1-fluorocyclobutyl)methyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1505]; N-((3-fluorooxetan-3-yl)methyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1506]; N-(cyclopropylmethyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1507]; (S)-N-(1-cyclopropylethyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1508]; (R)-N-(1-cyclopropylethyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1509]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1510]; 5-(1,8-naphthyridin-3-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1511]; 5-(1,8-naphthyridin-3-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1512]; N-cyclobutyl-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1513]; N-(3,3-difluorocyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1514]; N-(3,3-dimethylcyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1515]; 3-((5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1516]; N-(cis-3-Methoxycyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1517]; N-(trans-3-methoxycyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1518]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1519]; N-(cis-3-ethoxycyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1520]; N-(trans-3-ethoxycyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1521]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1522]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1523]; cis-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1524]; trans-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1525]; cis-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1526]; trans-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1527]; cis-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1528]; trans-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1529]; N-(cis-3-morpholinocyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1530]; N-(trans-3-morpholinocyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1531]; N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1532]; N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1533]; N-(4,4-difluorocyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1534]; cis-4-((5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1535]; (1s,4s)-4-((5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1536]; N-(cis-4-Methoxycyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1537]; N-(trans-4-Methoxycyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1538]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1539]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1540]; N-(cis-4-ethoxycyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1541]; N-(trans-4-ethoxycyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1542]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1543]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1544]; cis-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1545]; trans-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1546]; cis-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1547]; trans-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1548]; cis-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1549]; trans-N 1 -(5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1550]; N-(cis-4-morpholinocyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1551]; N-(trans-4-morpholinocyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1552]; N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1553]; N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1554]; N-(1-methylazetidin-3-yl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1555]; 5-(1,8-naphthyridin-3-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1556]; N-(1-methylpiperidin-4-yl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1557]; 5-(1,8-naphthyridin-3-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1558]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1559]; 5-(1,8-naphthyridin-3-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1560]; N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1561]; N-(1-methyl-1H-pyrazol-4-yl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1562]; N-Isopropyl-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1563]; N-Isobutyl-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1564]; N-(2-fluoro-2-methylpropyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1565]; N-(2,2-difluoropropyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1566]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1567]; (R)-5-(pyrido[2,3-b]pyrazin-7-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1568]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1569]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1570]; N-(2-Methoxyethyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1571]; (R)-N-(1-methoxypropan-2-yl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1572]; N-(2-isopropoxyethyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1573]; N-((1-methylcyclopropyl)methyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1574]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine and methane (1:1) [1575]; N-((1-fluorocyclobutyl)methyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1576]; N-((3-fluorooxetan-3-yl)methyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1577]; N-(cyclopropylmethyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1578]; (S)-N-(1-cyclopropylethyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1579]; (R)-N-(1-cyclopropylethyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1580]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1581]; N-(oxetan-3-ylmethyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1582]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1583]; N-cyclobutyl-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1584]; N-(3,3-difluorocyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1585]; N-(3,3-dimethylcyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1586]; 1-methyl-3-((5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1587]; N-(cis-3-Methoxycyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1588]; N-(trans-3-Methoxycyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1589]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1590]; N-(cis-3-ethoxycyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1591]; N-(trans-3-ethoxycyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1592]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1593]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1594]; cis-N 1 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1595]; trans-N 1 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1596]; cis-N 1 -methyl-N 3 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1597]; trans-N 1 -methyl-N 3 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1598]; cis-N 1 ,N 1 -Dimethyl-N 3 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1599]; trans-N 1 ,N 1 -Dimethyl-N 3 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1600]; N-(cis-3-morpholinocyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1601]; N-(trans-3-morpholinocyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1602]; N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1603]; N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1604]; N-(4,4-difluorocyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1605]; cis-4-((5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1606]; (1s,4s)-1-methyl-4-((5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1607]; N-(cis-4-Methoxycyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1608]; N-(trans-4-Methoxycyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1609]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1610]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1611]; N-(cis-4-ethoxycyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1612]; N-(trans-4-ethoxycyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1613]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1614]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1615]; cis-N 1 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1616]; trans-N 1 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1617]; cis-N 1 -methyl-N 4 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1618]; trans-N 1 -methyl-N 4 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1619]; cis-N 1 ,N 1 -Dimethyl-N 4 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1620]; trans-N 1 ,N 1 -Dimethyl-N 4 -(5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1621]; N-(cis-4-morpholinocyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1622]; N-(trans-4-morpholinocyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1623]; N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1624]; N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1625]; N-(1-methylazetidin-3-yl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1626]; N-(oxetan-3-yl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1627]; N-(1-methylpiperidin-4-yl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1628]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1629]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1630]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1631]; N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1632]; N-(1-methyl-1H-pyrazol-4-yl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1633]; N-Isopropyl-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1634]; N-isobutyl-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1635]; N-(2-fluoro-2-methylpropyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1636]; N-(2,2-difluoropropyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1637]; 5-(1,5-naphthyridin-2-yl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1638]; (R)-5-(1,5-naphthyridin-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1639]; 5-(1,5-naphthyridin-2-yl)-N-(3,3,3-trifluoropropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1640]; 5-(1,5-naphthyridin-2-yl)-N-(3,3,3-trifluoro-2,2-dimethylpropyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1641]; N-(2-Methoxyethyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1642]; (R)-N-(1-methoxypropan-2-yl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1643]; N-(2-isopropoxyethyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1644]; N-((1-methylcyclopropyl)methyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1645]; 5-(1,5-naphthyridin-2-yl)-N-((1-(trifluoromethyl)cyclopropyl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1646]; N-((1-fluorocyclobutyl)methyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1647]; N-((3-fluorooxetan-3-yl)methyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1648]; N-(cyclopropylmethyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1649]; (S)-N-(1-cyclopropylethyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1650]; (R)-N-(1-cyclopropylethyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1651]; N-(2-cyclopropyl-2,2-difluoroethyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1652]; 5-(1,5-naphthyridin-2-yl)-N-(oxetan-3-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1653]; 5-(1,5-naphthyridin-2-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1654]; N-cyclobutyl-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1655]; N-(3,3-difluorocyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1656]; N-(3,3-dimethylcyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1657]; 3-((5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1658]; N-(cis-3-Methoxycyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1659]; N-(trans-3-Methoxycyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1660]; N-(trans-3-(methoxymethyl)cyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1661]; N-(cis-3-ethoxycyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1662]; N-(trans-3-ethoxycyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1663]; N-(cis-3-(2-methoxyethoxy)cyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1664]; N-(trans-3-(2-methoxyethoxy)cyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1665]; cis-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1666]; trans-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclobutane-1,3-diamine [1667]; cis-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1668]; trans-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 -Methylcyclobutane-1,3-diamine [1669]; cis-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1670]; trans-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 3 ,N 3 -Dimethylcyclobutane-1,3-diamine [1671]; N-(cis-3-morpholinocyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1672]; N-(trans-3-morpholinocyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1673]; N-(cis-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1674]; N-(trans-3-(4-methylpiperazin-1-yl)cyclobutyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1675]; N-(4,4-difluorocyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1676]; cis-4-((5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1677]; (1s,4s)-4-((5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1678]; N-(cis-4-Methoxycyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1679]; N-(trans-4-Methoxycyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1680]; N-(cis-4-(difluoromethoxy)cyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1681]; N-(trans-4-(difluoromethoxy)cyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1682]; N-(cis-4-ethoxycyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1683]; N-(trans-4-ethoxycyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1684]; N-(cis-4-(2-methoxyethoxy)cyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1685]; N-(trans-4-(2-methoxyethoxy)cyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1686]; cis-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1687]; trans-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclohexane-1,4-diamine [1688]; cis-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1689]; trans-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 -Methylcyclohexane-1,4-diamine [1690]; cis-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1691]; trans-N 1 -(5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N 4 ,N 4 -Dimethylcyclohexane-1,4-diamine [1692]; N-(cis-4-morpholinocyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1693]; N-(trans-4-morpholinocyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1694]; N-(cis-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1695]; N-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1696]; N-(1-methylazetidin-3-yl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1697]; 5-(1,5-naphthyridin-2-yl)-N-(oxetan-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1698]; N-(1-methylpiperidin-4-yl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1699]; 5-(1,5-naphthyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1700]; N-(6,6-difluorospiro[3.3]heptan-2-yl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1701]; 5-(1,5-naphthyridin-2-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1702]; N-(2-methyl-2-azaspiro[3.3]heptan-6-yl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1703]; N-(1-methyl-1H-pyrazol-4-yl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1704]; cis-3-((5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1705]; (6-(2-((cis-3-hydroxycyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [1706]; cis-3-((5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1707]; cis-3-((5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1708]; cis-3-((5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1709]; cis-3-((5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1710]; cis-3-((5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1711]; cis-3-((5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1712]; cis-3-((5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1713]; cis-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1714]; cis-3-((5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1715]; cis-3-((5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1716]; cis-3-((5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1717]; cis-3-((5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1718]; cis-3-((5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1719]; cis-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1720]; cis-3-((5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1721]; cis-3-((5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1722]; cis-3-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1723]; cis-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1724]; cis-3-((5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1725]; cis-3-((5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1726]; cis-3-((5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1727]; cis-3-((5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1728]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1729]; (6-(2-((2-azaspiro[3.3]heptan-6-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [1730]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1731]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1732]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1733]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1734]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1735]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1736]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1737]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1738]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1739]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1740]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1741]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1742]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1743]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1744]; 5-(3-(2-Methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1745]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1746]; 5-(quinolin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1747]; 5-(quinoxalin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1748]; 5-(4-Methoxyquinazolin-6-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1749]; 5-(1,8-naphthyridin-3-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1750]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1751]; 5-(1,5-naphthyridin-2-yl)-N-(2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1752]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1753]; (6-(2-((2-isobutyl-2-azaspiro[3.3]heptan-6-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [1754]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1755]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1756]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1757]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1758]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1759]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1760]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1761]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1762]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1763]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1764]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1765]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1766]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1767]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1768]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1769]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(1-methyl-1H-benzo[2-isobutyl-2-azaspiro[3.3]heptan-6-yl] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1770]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1771]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1772]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1773]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1774]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1775]; N-(2-isobutyl-2-azaspiro[3.3]heptan-6-yl)-5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1776]; 5-(imidazo[1,2-a]pyridin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1777]; Pyrrolidin-1-yl(6-(2-((cis-4-(trifluoromethoxy)cyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)methanone [1778]; 5-(imidazo[1,2-b]pyridazin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1779]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1780]; 5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1781]; 5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1782]; 5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1783]; 5-(4-Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1784]; 5-(1-Isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1785]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1786]; 5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1787]; 5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1788]; 5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1789]; 5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1790]; 5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1791]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1792]; 5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1793]; 5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1794]; 5-(Quinolin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1795]; 5-(quinoxalin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1796]; 5-(4-Methoxyquinazolin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1797]; 5-(1,8-naphthyridin-3-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1798]; 5-(pyrido[2,3-b]pyrazin-7-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1799]; 5-(1,5-naphthyridin-2-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1800]; N-(2-fluoro-2-methylpropyl)-5-(3-isopropyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1801]; 5-(imidazo[1,2-a]pyrimidin-6-yl)-N-(cis-4-(methoxy-d 3 )Cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1802]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(methoxy-d 3 )Cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1803]; cis-3-((5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1804]; (6-(2-((cis-3-hydroxy-3-methylcyclobutyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)imidazo[1,2-a]pyridin-3-yl)(pyrrolidin-1-yl)methanone [1805]; cis-3-((5-(imidazo[1,2-b]pyridazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1806]; cis-3-((5-(imidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1807]; cis-3-((5-(3-chloroimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1808]; cis-1-methyl-3-((5-(3-methylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1809]; cis-3-((5-(3-ethylimidazo[1,2-a]pyrimidin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1810]; cis-3-((5-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1811]; cis-3-((5-(1-isopropyl-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1812]; cis-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1813]; cis-3-((5-(1-(3,3-difluorocyclobutyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1814]; cis-1-methyl-3-((5-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1815]; cis-3-((5-(2,3-dimethyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1816]; cis-3-((5-(3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1817]; cis-3-((5-(3-(2-fluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1818]; cis-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1819]; cis-3-((5-(3-(2-methoxyethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1820]; cis-1-methyl-3-((5-(1-methyl-1H-benzo[a]methyl] [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1821]; cis-1-methyl-3-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1822]; cis-1-methyl-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1823]; cis-3-((5-(4-methoxyquinazolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1824]; cis-3-((5-(1,8-naphthyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1825]; cis-1-methyl-3-((5-(pyrido[2,3-b]pyrazin-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutan-1-ol [1826]; cis-3-((5-(1,5-naphthyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1827]; trans-4-((5-(imidazo[1,2-a]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1828]; cis-4-((5-(3-isobutyl-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1829]; (R)-2-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)propan-1-ol [1830]; (R)-1-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)propan-2-ol [1831]; (S)-1-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)propan-2-ol [1832]; 1-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-methylpropan-2-ol [1833]; (cis-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)methanol [1834]; trans-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutan-1-ol [1835]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(7-methyl-7-azaspiro[3.5]nonan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1836]; (cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanol [1837]; N-(cis-4-(2,2-difluoroethoxy)cyclohexyl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1838]; 2-((cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)oxy)ethan-1-ol [1839]; trans-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1840]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-((4-methylpiperazin-1-yl)methyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1841]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-(morpholinomethyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1842]; Ethyl cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexane-1-carboxylate [1843]; N-(trans-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)acetamide [1844]; cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N-dimethylcyclohexane-1-carboxamide [1845]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-methyl-2-azaspiro[3.5]nonan-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1846]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1,4-dioxaspiro[4.5]decan-8-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1847]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((4-methylmorpholin-2-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1848]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(2-fluoroethyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1849]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(2,2-difluoroethyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1850]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(3,3,3-trifluoropropyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1851]; 2-(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)ethan-1-ol [1852]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1853]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1854]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4S)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1855]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1856]; 1-(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)ethan-1-one [1857]; 1-(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)propan-1-one [1858]; 1-(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)-2-methylpropan-1-one [1859]; Cyclopropyl((4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone [1860]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(methylsulfonyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1861]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1862]; (R)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1863]; (S)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1864]; (3R,4R)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)tetrahydro-2H-pyran-3-ol [1865]; (3S,4R)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)tetrahydro-2H-pyran-3-ol [1866]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-methoxytetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1867]; cis-1-methyl-4-((5-(2-methyl-3-(2,2,2-trifluoroethyl)-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1868]; 3-(5-(2-((cis-4-hydroxy-4-methylcyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-2,2-dimethylpropanenitrile [1869]; 1-(5-(2-((4,4-difluorocyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-2-methylpropan-2-ol [1870]; 2-Methyl-1-(2-methyl-5-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)-3H-imidazo[4,5-b]pyridin-3-yl)propan-2-ol [1871]; 2-(5-(2-((cis-4-hydroxy-4-methylcyclohexyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-N,N-dimethylacetamide [1872]; 5-(3-(azetidin-3-ylmethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(4,4-difluorocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1873]; N-(4,4-difluorocyclohexyl)-5-(2-methyl-3-((1-methylazetidin-3-yl)methyl)-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1874]; cis-1-methyl-4-((5-(2-methyl-3-(oxetan-3-ylmethyl)-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1875]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(cis-4-(methoxy-d 3 )cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1876]; N-(cis-4-(2,2-difluoroethoxy)cyclohexyl)-5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1877]; 2-((cis-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)oxy)ethan-1-ol [1878]; trans-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1879]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1,4-dioxaspiro[4.5]decan-8-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1880]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-(2-fluoroethyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1881]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-(2,2-difluoroethyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1882]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-(3,3,3-trifluoropropyl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1883]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1884]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1885]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3S,4S)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1886]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-((3R,4S)-3-fluoro-1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1887]; 1-(4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)-2-methylpropan-1-one [1888]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1889]; trans-4-((5-(1-(2,2-difluoroethyl)-1H-benzo [d][1,2,3]triazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1890]; trans-1-methyl-4-((5-(pyrazolo[1,5-a]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexan-1-ol [1891]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1892]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(trans-3-morpholinocyclobutyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1893]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(cis-4-((3-fluoroazetidin-1-yl)methyl)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1894]; trans-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N-dimethylcyclohexane-1-carboxamide [1895]; Azetidin-1-yl(cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanone [1896]; (cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)(pyrrolidin-1-yl)methanone [1897]; N-(cis-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)acetamide [1898]; 1-(7-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonan-2-yl)ethan-1-one [1899]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-4-fluoro-1-methylpyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1900]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4S)-4-fluoro-1-methylpyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1901]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4R)-4-fluoro-1-methylpyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1902]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-4-fluoro-1-methylpyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1903]; (S)-1-(3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)pyrrolidin-1-yl)ethan-1-one [1904]; (R)-1-(3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)pyrrolidin-1-yl)ethan-1-one [1905]; (3S,4R)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)tetrahydrofuran-3-ol [1906]; (3R,4S)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)tetrahydrofuran-3-ol [1907]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-fluoro-1-isobutylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1908]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-3-fluoro-1-isobutylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1909]; 1-(4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)ethan-1-one [1910]; (S)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylpiperidin-2-one [1911]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1912]; N-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1913]; N-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1914]; (R)-N-(4,4-difluorocyclohexyl)-5-(1-((5-(1-fluoroethyl)-1,3,4-oxadiazol-2-yl)methyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1915]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1916]; (S)-(2,2-Difluorocyclopropyl)(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone [1917]; (R)-(2,2-Difluorocyclopropyl)(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone [1918]; N-((1s,3s)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)acetamide [1919]; N-((1r,3r)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)acetamide [1920]; (1r,3r)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N,1-trimethylcyclobutane-1-carboxamide [1921]; (1s,3s)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N,1-trimethylcyclobutane-1-carboxamide [1922]; ((1s,3s)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)(pyrrolidin-1-yl)methanone [1923]; ((1r,3r)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)(pyrrolidin-1-yl)methanone [1924]; 1-(2-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-7-azaspiro[3.5]nonan-7-yl)ethan-1-one [1925]; 1-((3aR,5s,6aS)-5-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethan-1-one [1926]; 1-((3aR,5r,6aS)-5-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethan-1-one [1927]; 1-(7-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonan-2-yl)ethan-1-one [1928]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-N-(2-oxaspiro) [3.5]nonan-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1929]; N-((1s,3s)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)acetamide [1930]; N-((1r,3r)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)acetamide [1931]; N-((1s,3s)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)propionamide [1932]; N-((1r,3r)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)propionamide [1933]; (1s,3s)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N,1-trimethylcyclobutane-1-carboxamide [1934]; (1r,3r)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N,1-trimethylcyclobutane-1-carboxamide [1935]; ((1s,3s)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)(pyrrolidin-1-yl)methanone [1936]; ((1r,3r)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)(pyrrolidin-1-yl)methanone [1937]; 1-((1s,3s)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)pyrrolidin-2-one [1938]; 1-((1r,3r)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)pyrrolidin-2-one [1939]; 1-((3S,4R)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoropyrrolidin-1-yl)ethan-1-one [1940]; 1-((3R,4S)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoropyrrolidin-1-yl)ethan-1-one [1941]; 1-((3R,4R)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoropyrrolidin-1-yl)ethan-1-one [1942]; 1-((3S,4S)-3-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoropyrrolidin-1-yl)ethan-1-one [1943]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-4-fluoro-1-(oxetan-3-yl)pyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1944]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-4-fluoro-1-(oxetan-3-yl)pyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1945]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4R)-4-fluoro-1-(oxetan-3-yl)pyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1946]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4S)-4-fluoro-1-(oxetan-3-yl)pyrrolidin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1947]; N-((1s,4s)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexyl)acetamide [1948]; N-((1r,4r)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexyl)acetamide [1949]; (3,3-Difluoroazetidin-1-yl)((1s,4s)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclohexyl)methanone [1950]; 1-((3S,4R)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-3-fluoropiperidin-1-yl)ethan-1-one [1951]; 1-((3R,4S)-4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-3-fluoropiperidin-1-yl)ethan-1-one [1952]; (4,4-Difluorocyclohexyl)(4-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)piperidin-1-yl)methanone [1953]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4R)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1954]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1955]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3R,4R)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1956]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1957]; 1-(2-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-7-azaspiro[3.5]nonan-7-yl)ethan-1-one [1958]; 1-((3aR,5s,6aS)-5-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethan-1-one [1959]; 1-((3aR,5r,6aS)-5-((5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethan-1-one [1960]; 5-(3-(2,2-difluoroethyl)-2-methyl-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-oxaspiro) [3.5]nonan-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1961]; N-((1s,3s)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)acetamide [1962]; N-((1r,3r)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)acetamide [1963]; (1s,3s)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N,1-trimethylcyclobutane-1-carboxamide [1964]; (1r,3r)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-N,N,1-trimethylcyclobutane-1-carboxamide [1965]; ((1s,3s)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)(pyrrolidin-1-yl)methanone [1966]; ((1r,3r)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)(pyrrolidin-1-yl)methanone [1967]; 1-((1s,3s)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)pyrrolidin-2-one [1968]; 1-((1r,3r)-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)pyrrolidin-2-one [1969]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine[1970]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-5-yl)-N-(cis-4-(trifluoromethoxy)cyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1971]; N-((1s,4s)-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexyl)acetamide [1972]; N-((1r,4r)-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexyl)acetamide [1973]; (1s,4s)-4-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclohexan-1-ol [1974]; 1-(2-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-7-azaspiro[3.5]nonan-7-yl)ethan-1-one [1975]; 1-((3aR,5s,6aS)-5-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethan-1-one [1976]; 1-((3aR,5r,6aS)-5-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethan-1-one [1977]; 1-(7-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-2-azaspiro[3.5]nonan-2-yl)ethan-1-one [1978]; 5-(1-(2,2-difluoroethyl)-2-methyl-1H-imidazo[4,5-b]pyrazin-6-yl)-N-(2-oxaspiro) [3.5]nonan-7-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine [1979]; N-((1r,3r)-1-methyl-3-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide [1980]; N-((1r,3r)-1-methyl-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide [1981]; N-(cis-3-((5-(1-(2,2-difluoroethyl)-2-methyl-1H-benzo[d]imidazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)-1-methylcyclobutyl)acetamide [1982]; N-(trans-1-methyl-3-((5-(pyrazolo[1,5-a]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide [1983]; N-(cis-1-methyl-3-((5-(quinolin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide [1984]; 2-Methoxy-N-(trans-1-methyl-3-((5-(quinoxalin-6-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)amino)cyclobutyl)acetamide [1985] 2. The compound of claim 1, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

12. 12. A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

13. 12. A composition for treating a disorder or disease in a patient selected from the group consisting of neuropathy, diabetes, and cancer, comprising a compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof.

14. 14. The composition of claim 13, wherein the disorder or disease is diabetes.

15. 14. The composition of claim 13, wherein the cancer is selected from the group consisting of brain tumor, glioblastoma, ovarian cancer, breast cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, pancreatic cancer, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, and chronic myeloid leukemia.

16. 14. The composition of claim 13, wherein the disorder or disease is a neurological disorder, and the neurological disorder is selected from the group consisting of Alzheimer's disease, amyotrophic lateral sclerosis, CDKL5 deficiency disorder, Down's syndrome, frontotemporal dementia with parkinsonism-17 (FTDP-17), dementia with Lewy bodies, Parkinson's disease, Pick's disease, and further diseases with significant neurodegeneration, such as autism, dementia, epilepsy, Huntington's disease, multiple sclerosis; diseases and disorders associated with acquired brain injury, such as chronic traumatic encephalopathy, traumatic brain injury, tumor, stroke, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, globular glial tauopathy, primary age-related tauopathy, neurofibrillary tangle dementia, chronic traumatic encephalopathy (CTE), frontotemporal lobar degeneration with tau inclusions (FTLD-tau), and age-related tauastrogliopathy.

17. 14. The composition of claim 13, wherein the disorder or disease is Alzheimer's disease.

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