Bicyclic heteroaromatic compounds for treating neurological disorders

Abstract

This disclosure provides compounds and pharmaceutically acceptable salts thereof that are useful, for example, for treating neurological disorders in subjects. This disclosure also provides compositions containing the same, as well as methods for using and preparing the same. This specification provides a method for treating a subject that requires treatment of a neurological disorder, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (V), or (VI), or any of its subformulas, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable composition provided herein.

Description

[Technical Field]

[0001] This disclosure provides compounds and pharmaceutically acceptable salts thereof that are useful, for example, for treating neurological disorders in a subject. This disclosure also provides compositions containing the same, as well as methods for using and preparing the same.

[0002] Sequence List This application includes a sequence listing submitted electronically as an XML file named "50887-0043WO1.XML". The XML file, created on June 12, 2024, is 4,096 bytes in size. The contents of the XML file are incorporated herein by reference in their entirety.

[0003] Parties to the joint research agreement The subject matter described herein was created in accordance with a collaborative research agreement between Prothena Biosciences Limited and Vanderbilt University that was in effect on or prior to the date the subject matter described herein was created, and the subject matter was created as a result of activities undertaken within the scope of the collaborative development agreement.

[0004] Priority Claim This application is a U.S. provisional patent application with reference numbers 63 / 508,131, 63 / 508,137, 63 / 508,139, 63 / 510,695, and 63 / 510,695, filed on June 28, 2023. Claiming the interests of U.S. Provisional Patent Application No. 63 / 510,696, U.S. Provisional Patent Application No. 63 / 510,711 filed on 28 June 2023, U.S. Provisional Patent Application No. 63 / 656,038 filed on 4 June 2024, and U.S. Provisional Patent Application No. 63 / 656,070 filed on 4 June 2024, each of which is incorporated herein by reference in whole. [Background technology]

[0005] Bispecific tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a 763-amino acid, 85-kDa serine / threonine / tyrosine kinase located on chromosome 21 (21q22.2). DYRK1A possesses catalytic activity regulated by autophosphorylation of the tyrosine residue (Y321), which results in constitutively activated serine / threonine kinase activity. See Abbassi, et al., Pharmacology & Therapeutics, 151, 87-98 (2015). Because DYRK1A is constitutively active, its activity is dose-dependent. Therefore, both elevated and decreased levels of DYRK1A (compared to wild-type levels) have been shown to cause neurological disorders. See Duchon and Herault, Front Behav. Neurosci. 10, 104-104 (2016). DYRK1A is also a member of the large CMGC kinase family, which includes cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPKs), glycogen synthase kinases (GSKs), and CDC-like kinases (CLKs).

[0006] Furthermore, DYRK1A has been shown to play a role in cell cycle regulation by phosphorylating (and therefore inhibiting) the activated T cell nuclear factor (NFAT) transcription factor family, at least partially. In addition, more than 20 substrates of DYRK1A have been identified, including those involved in cell signaling, chromatin regulation, gene expression, alternative splicing, cytoskeleton, and synaptic function. See Abassi, et al, (2016). DYRK1A dysregulation is associated with various disease conditions, such as Alzheimer's disease, autism, and Down syndrome. In some cases, novel mutations in DYRK1A are associated with autistic phenotypes. See, for example, Dang, et al., Molecular Psychiatry, 23, 747-758 (2018).

[0007] DYRK1A is also known to play an important role in brain development. For example, a decrease in DYRK1A activity during neurodevelopment (it has a single copy of a loss-of-function mutation) results in an intellectual disability phenotype. Conversely, trisomy 21 in individuals with Down syndrome is associated with triploidy of the DYRK1A gene, which results in increased DYRK1A activity. DYRK1A is located on chromosome 21, specifically within the "Down syndrome region," which is a part of chromosome 21 containing genes particularly associated with the development of the Down syndrome phenotype. As a result, individuals with Down syndrome have three copies of DYRK1A, and because DYRK1A is dose-sensitive, elevated DYRK1A levels in such individuals significantly affect the localization and function of the DYRK1A protein. DYRK1A expression is also elevated in the CNS of individuals with neurodegenerative diseases, such as Parkinson's disease, Pick's disease, and Alzheimer's disease.

[0008] Furthermore, approximately 50% of individuals with Down syndrome eventually develop Alzheimer's disease, with symptoms typically beginning between the ages of 40 and 60. DYRK1A phosphorylates amyloid precursor protein (APP), promoting the production of pathogenic amyloid-beta peptide (Aβ). Dyrk1A also phosphorylates tau both directly and indirectly (see Abassi, et al, (2016)). Both amyloid-beta and tau pathologies are associated with the Down syndrome phenotype.

[0009] Normalizing the DYRK1A gene load by crossing Ts65Dn mice (DS model) with DYRK1A knockout mice reverses many Alzheimer's disease-like phenotypes. See Garcia-Cerro et al., 2017. In individuals with Down syndrome, DYRK1A mRNA levels, protein levels, and kinase activity increase by approximately 50%, reflecting the gene copy number. See Liu et al., 2008, and also Wegiel et al., 2011.

[0010] Because there are no available treatments for these neurological disorders, the prognosis for individuals with Alzheimer's disease, for example, is poor. This can be particularly devastating because Alzheimer's disease causes a sharp decline in the survival rate of individuals with Down syndrome who live past the age of 45. Only about 25% of individuals with Down syndrome survive past the age of 60, and most of them develop Alzheimer's disease.

[0011] Dementia remains a critically unmet medical need for all individuals and places a significant burden on public health. Currently, one in three older adults develops dementia, and approximately 70% of dementia cases are attributed to Alzheimer's disease. About 11% of Americans over 65 have AD, and this number exceeded 6.2 million in 2021. This figure is projected to exceed 12 million by 2050 (www.Alz.org). Currently, there are no approved therapies for treating Alzheimer's disease associated with Down syndrome, which represents a significant unmet medical need. While some DYRK1A inhibitors have been tested in vitro or in preclinical animal models for treating Alzheimer's disease or Down syndrome, identifying compounds that selectively target DYRK1A has proven challenging because DYRK1A is a member of the highly conserved CMGC kinase family. Therefore, identifying DYRK1A inhibitors for treating Down syndrome, Alzheimer's disease, Alzheimer's disease associated with Down syndrome, and other neurodegenerative and neurological disorders remains a necessity. [Prior art documents] [Non-patent literature]

[0012] [Non-Patent Document 1] Abbassi,et al.,Pharmacology&Therapeutics,151,87-98(2015) [Non-Patent Document 2] Duchon and Herault, Front Behav. Neurosci. 10, 104 - 104(2016)

Non - Patent Document 3

Non - Patent Document 4

Summary of the Invention

[0013] Some embodiments are of the structure of formula (I):

Chemical formula

Chemical formula

Chemical formula

[0014] Some embodiments involve compounds of formula (II). [ka] or a pharmaceutically acceptable salt thereof (in the formula, each [ka] Y 1 , Y 2 , and Y 3 A bicyclic ring system containing ((i)Y 1 CR 3 Y 2 (ii) Y 1 S is Y 2 This represents a single or double bond such that (C) is the case; Y 3 N and CR 4 Selected from; Ring B is selected from (a), (b), and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); (b) [ka] (X 2 S and NR 7 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] This represents single or double bonds such that ring B forms an aromatic bicyclic ring system. R 1 is hydrogen, C 1-4 -C(O)C optionally substituted with alkyl and one or more halogens. 3-6 Selected from cycloalkyl groups; R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R 10 ) Selected from NO2 and -CN; R 3 and R 4 These are, independently, hydrogen, halogen, and C. 1-4 Alkyl and C 1-4 Selected from haloalkyl; R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 -CN, -S(O)2C 1-4 Alkyl, C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl groups, however, Y 1 CR 3 Y 2 If it is N, then R A is -OR 11Further selections are made from these. Y 1 CR 3 Y 2 N is Y 3 is CH, ring B is (a), p is 0, X 1 If is N and ring A is 1-fluoro-1-tetrahydropyranyl, then R A It is further selected from hydrogen, Y 1 S is Y 2 C is X 1 If it is N, then R A It is further selected from hydrogen; Ring A is, C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of which is substituted with one or more halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle); C 7-12 Carbon rings and 7-12 membered heterocycles (each of these being halogens, C) 1-6 Alkyl, C1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle, provided that if ring B is selected from (b), then ring A is not chroman. Selected from; However, if one or more of (i), (ii), (ii), (iv), and (v) apply, then ring A is C 4-6 Further selections are made from carbon rings and 3- to 6-membered heterocycles, each of which is C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles: (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 It is alkyl; and (vi) Ring B is (c); However, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl; R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R13 , -C(O)OR 13 ,-OC(O)R 13 ,-C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -N(R 13 )S(O)2(R 13 ), -S(O)2R 13 -S(O)2N(R 13 ) Selected from -NO2 and -CN, however, R A ga-OR 11 If that is the case, then R 5 is -OR 13 Not; R 6 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14 -S(O)2N(R 14 )2, -NO2, =O, and -CN are selected; R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14-S(O)2N(R 14 )2, -NO2, =O, and -CN are selected; R 7 and R 9 These are, independently, hydrogen and C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups; m is selected from 0, 1, and 2; p is selected from 0, 1, and 2; q is selected from 0, 1, and 2; (r is selected from 0, 1, and 2) To provide.

[0015] Some embodiments include compounds of formula (V): [ka] or a pharmaceutically acceptable salt thereof (in the formula, Q 1 is N, S, O or CR 3 Q 2 is N or C, and Q 3 is N or CR 4 Q 4 is N or CR 3 Q 5 is C or N, and each [ka] Q 1 Q 2 Q 3 Q 4 , and Q 5The bicyclic ring system containing is single or double bonded such that it becomes benzo[d]thiazole, benzo[d]xazole, imidazo[1,2-a]pyridine, thiazolo[5,4-b]pyridine, imidazo[1,2-b]pyridazine, pyrazolo[1,5-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, or [1,2,4]triazolo[1,5-b]pyridazine; R A is halogen, -OR 10 , -SR 10 , -N(R 10 )2, -CN, one or more halogens or -OR 10 C arbitrarily replaced by 1-6 Alkyl, C 3- Selected from C6 saturated cycloalkyls and 3- to 6-membered saturated heterocycloalkyls; Ring A is C3-C 10 Saturated cycloalkyl, C3-C 10 Selected from partially saturated carbocyclic rings, 3-10 member saturated heterocycloalkyl groups, and 3-10 member partially saturated heterocyclic rings, each of which is, Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R 11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R 11 -NO2, and =O; Halogen, -OR 11 , -SR 11 , -N(R11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R 11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R 11 C is optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R 11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R 11(Optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN) Optionally substituted with one or more substituents independently selected from; Ring B is C3-C 10 Selected from carbocyclic rings and 3- to 12-membered heterocycles, each of these is Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R12 )2, -S(O)(NR 12 )R 12 C is optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 (Optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN) Optionally substituted with one or more substituents independently selected from; R 1 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and -C(O)R 13 Selected from; R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 ) Selected from -NO2 and -CN; R 3Independently, hydrogen, halogen, and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 4 is hydrogen, halogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-4 Alkyl, C 1-4 Selected from haloalkyls and cycloalkyls optionally substituted with one or more halogens; n is selected from 0, 1, and 2; However, if ring B is pyrazolyl, then ring A is not N-Boc pyrrolidinyl. To provide.

[0016] Some embodiments involve compounds of formula (VI): [ka] or a pharmaceutically acceptable salt thereof (in the formula, Q 1 is S or CR 3 Q 2 is N or C, and Q 3 N and CR 4 Selected from each [ka] Q 1 Q 2 , and Q 3 The bicyclic ring system containing represents a single or double bond such that it becomes benzo[d]thiazole, imidazo[1,2-a]pyridine, thiazolo[5,4-b]pyridine, or imidazo[1,2-b]pyridazine; R A is halogen, -OR 10 , -SR 10 , -N(R 10)2, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3- Selected from C6 saturated cycloalkyls and 3- to 6-membered saturated heterocycloalkyls; Ring A is C3-C 10 Saturated cycloalkyl, C3-C 10 Selected from partially saturated carbocyclic rings, 3-10 member saturated heterocycloalkyl groups, and 3-10 member partially saturated heterocyclic rings, each of which is, Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R 11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R 11 -NO2, and =O; Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R 11 C is optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R 11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R 11 (Optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN) Optionally substituted with one or more substituents independently selected from; Ring B is C3-C 10 Selected from carbocyclic rings and 3- to 12-membered heterocycles, each of these is Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12)2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 C is optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 (Optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN) Optionally substituted with one or more substituents independently selected from; R 1 is hydrogen, C 1-4 Alkyl and -C(O)R 13 Selected from; R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 ) Selected from -NO2 and -CN; R 3 and R 4 These are hydrogen, halogen, and C, respectively. 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-4 Alkyl, C 1-4 Selected from haloalkyls and cycloalkyls optionally substituted with one or more halogens; n is selected from 0, 1, and 2; However, if ring B is pyrazolyl, then ring A is not N-Boc pyrrolidinyl. To provide.

[0017] Furthermore, this specification provides pharmaceutical compositions comprising compounds of formula (I), (II), (III), (IV), (V), or (VI), or any of their subformulas, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable carriers.

[0018] This specification provides a method for treating a neurological disorder in a subject requiring treatment, the method comprising administering a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (V), or (VI), or any of its subformulas, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, to the subject.

[0019] Some embodiments provide a method for treating a neurological disorder in a subject requiring treatment, the method comprising: (a) determining that the neurological disorder is related to dysregulation of the expression, activity or level of the DYRK1A gene, the DYRK1A protein, or any of them; and (b) administering a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (V), or (VI), or any of its subformulas, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, to the subject.

[0020] Furthermore, this specification provides a method for treating a neurological disorder in a subject requiring treatment, the method comprising: (a) determining that the neurological disorder is a DYRK1A-related neurological disorder; and (b) administering a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (V), or (VI), or any of its subformulas, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, to the subject.

[0021] Furthermore, this specification provides a method for treating a subject in need of treatment for a neurological disorder, the method comprising: (a) determining that the subject has a neurological disorder; and (b) administering to the subject a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (V), or (VI), or any of its subformulas, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein.

[0022] This specification provides a method for treating a DYRK1A-related disorder in a subject, the method comprising administering to a subject previously determined to have a DYRK1A-related disorder a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (V), or (VI), any subformula thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable composition provided herein.

[0023] This specification provides a method for treating a subject, the method comprising administering a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (V), or (VI), or any of its subformulas, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, to a subject having a clinical record indicating that the subject has dysregulation of the expression, activity, or level of the DYRK1A gene, the DYRK1A protein, or any of the thereof.

[0024] The disclosure also provides a method for inhibiting DYRK1A activity i in mammalian cells, the method comprising contacting mammalian cells with a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (V), or (VI), any subformula thereof, or a pharmaceutically acceptable salt thereof.

[0025] Details of one or more embodiments of this disclosure are described in the accompanying drawings and the following description. Other features and advantages of this disclosure will become apparent from the description and the claims.

[0026] Additional definitions To facilitate understanding of the Disclosure as defined herein, several additional terms are defined below. In general, the nomenclature used herein and the testing procedures in organic chemistry, medicinal chemistry, and pharmacology described herein are well known and commonly used in the art. Unless otherwise specified, all technical and scientific terms used herein generally have the same meaning as commonly understood by experts in the art to which this Disclosure pertains. Each of the patents, applications, published applications, and other publications referenced throughout this specification and its appendices are incorporated herein by reference in their entirety. In case of any conflict, this specification, including its definitions, shall prevail.

[0027] The term "approximately" means that, when referring to a number or range of numbers, the number or range referred to is an approximation, for example, within the range of experimental variation and / or statistical experimental error, and therefore the number or range of numbers may vary by up to ±10% of the stated number or range of numbers.

[0028] With respect to formulations, compositions, or components, the term “acceptable,” as used herein, means that it does not have any permanent adverse effects on the overall health of the subject being treated.

[0029] The term "inhibit" or "inhibit" means to reduce by a measurable amount or to prevent it entirely (e.g., 100% inhibition).

[0030] The term “therapeutic effective dose” means an amount of the compound sufficient, when administered to a subject in need of such treatment, to (i) treat a neurological disorder as described herein, (ii) reduce, improve, or eliminate one or more symptoms of a particular neurological disorder, or (iii) delay the onset of one or more symptoms of a particular neurological disorder as described herein. In some embodiments, the therapeutic effective dose is an amount sufficient to inhibit DYRK1A activity in brain tissue.

[0031] As used herein, the terms “to treat” or “treatment” refer to therapeutic or palliative measures. Beneficial or desired clinical outcomes include, but are not limited to, a total or partial reduction of symptoms associated with neuropathy, whether detectable or undetectable; a reduction in the degree of neuropathy; a stabilized (i.e., non-worsening) state of neuropathy; delaying or slowing disease progression; improvement or mitigation of the disease state (e.g., one or more symptoms of neuropathy); and remission (whether partial or total), and may be determined by a variety of clinical assessments, including clinical evaluations and self-reports. “Treatment” may also mean an extension of survival compared to the expected survival without treatment.

[0032] The term “medicinal excipient” means a medicinal material, composition, or vehicle, such as a liquid or solid filler, diluent, carrier, solvent, or encapsulating material. In one embodiment, each component is “medicinal” in the sense that it is compatible with the other components of a pharmaceutical formulation and is suitable for use in contact with human and animal tissues or organs in proportion to a reasonable benefit-risk ratio, within the bounds of sound medical judgment, without causing excessive toxicity, irritation, allergic reactions, immunogenicity, or other problems or complications. For example, Remington: The Science and Practice of Pharmacy, 21st ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2005, Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et al., Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009, Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Gower Publishing Company: 2007, Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson ed.; CRC Press LLC: Boca Raton, FL, 2009.

[0033] The term “pharmacovigilantly acceptable salt” refers to a formulation of a compound that does not cause significant irritation to the organism to which it is administered and does not neutralize the biological activity and properties of the compound. In certain cases, pharmacovigilantly acceptable salts are obtained by reacting the compounds described herein with acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. In some examples, pharmacovigilantly acceptable salts are obtained by reacting the acidic group-containing compounds described herein with a base to form salts, e.g., ammonium salts, alkali metal salts, e.g., sodium or potassium salts, alkaline earth metal salts, e.g., calcium or magnesium salts, organic bases, e.g., salts of dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, and salts with amino acids, e.g., arginine, lysine, etc., or by other methods previously determined. Pharmacovigilantly acceptable salts are not particularly limited insofar as they can be used in pharmaceuticals. Examples of salts formed by the compounds described herein with bases include: salts thereof with inorganic bases, such as sodium, potassium, magnesium, calcium, and aluminum; salts thereof with organic bases, such as methylamine, ethylamine, and ethanolamine; salts thereof with basic amino acids, such as lysine and ornithine; and ammonium salts. Salts may include: mineral acids, such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid; and organic acids, such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; and acidic amino acids, such as acid addition salts particularly exemplified by acid addition salts with aspartic acid and glutamic acid.

[0034] The term “pharmaceutical composition” refers to a mixture of the compounds described herein with other chemical components (collectively referred to herein as “pharmaceutically acceptable carriers”), such as stabilizers, diluents, dispersants, suspending agents, thickeners, and / or other excipients. Pharmaceutical compositions facilitate the administration of compounds to living organisms.

[0035] The term "subject" refers to animals including, but not limited to, primates (e.g., humans), monkeys, cattle, pigs, sheep, goats, horses, dogs, cats, rabbits, rats, or mice. The terms "subject" and "patient" are used interchangeably herein in reference to mammalian subjects, such as humans.

[0036] The terms "halo" and "halogen" refer to fluoro(F), chloro(Cl), bromo(Br), or iodine(I).

[0037] The term "oxo" refers to a divalent double-bonded oxygen atom (i.e., "=O"). As used herein, the oxo group is bonded to a carbon atom to form a carbonyl group.

[0038] The term "hydroxyl" refers to the -OH radical.

[0039] The term "nitro" refers to the -NO2 radical.

[0040] The term "cyano" refers to the -CN radical.

[0041] The term "alkyl" refers to a saturated acyclic hydrocarbon radical that contains the indicated number of carbon atoms and may be linear or branched. For example, C 1-10 This indicates that the group may have 1 to 10 carbon atoms (including endpoints) within it. Non-limiting examples include methyl, ethyl, iso-propyl, tert-butyl, and n-hexyl. The term “saturated,” when used in this context, means that only single bonds exist between the constituent carbon atoms, and other available valencies are occupied by hydrogen and / or other substituents as defined herein.

[0042] The "alkylene" group is a divalent alkyl group as described herein.

[0043] The term "haloalkyl" refers to an alkyl group in which one or more hydrogen atoms are independently replaced by a halogen.

[0044] The term "hydroxyalkyl" refers to an alkyl group in which one or more hydrogen atoms are replaced by hydroxyl groups as defined herein.

[0045] The term "alkoxy" refers to an -O-alkyl radical (e.g., -OCH3).

[0046] The terms “carbocyclic” and “carbocyclyl” refer to monocyclic, bicyclic, tricyclic, or polycyclic groups of 3 to 20 carbon atoms, which may be fully saturated, partially unsaturated, aromatic, and (in polycyclic systems) any combination thereof. Carbocyclyl groups may include condensed, cross-linked, and spirocyclic systems. In some embodiments, the carbocyclyl is an aryl as defined herein. Examples of carbocyclyl groups include aryl and cycloalkyl groups as described herein.

[0047] The term "aryl" refers to a monocyclic, bicyclic, tricyclic, or polycyclic group of 6 to 20 carbon atoms in which at least one ring in the system is aromatic (e.g., a 6-carbon monocyclic, 10-carbon bicyclic, or 14-carbon tricyclic aromatic ring system). Examples of aryl groups include phenyl, naphthyl, and tetrahydronaphthyl.

[0048] The term "cycloalkyl," as used herein, refers to a cyclic saturated or partially unsaturated hydrocarbon group having, for example, 3 to 20 ring carbons, preferably 3 to 16 ring carbons, and more preferably 3 to 12 ring carbons, or 3 to 10 ring carbons, or 3 to 6 ring carbons. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Cycloalkyl groups may include condensed and crosslinked ring systems. Non-limiting examples of condensed / crosslinked cycloalkyls include bicyclo[1.1.0]butane, bicyclo[2.1.0]pentane, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, bicyclo[2.1.1]hexane, bicyclo[3.2.0]heptane, bicyclo[4.1.0]heptane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[4.2.0]octane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, and others. Cycloalkyl groups may also include spirocyclic rings (e.g., spirocyclic bicycles in which two rings are connected by only one atom). Non-limiting examples of spirocyclic cycloalkyls include spiro[2.2]pentane, spiro[2.5]octane, spiro[3.5]nonane, spiro[3.5]nonane, spiro[3.5]nonane, spiro[4.4]nonane, spiro[2.6]nonane, spiro[4.5]decane, spiro[3.6]decane, and spiro[5.5]undecane.

[0049] The terms “heterocyclic” and “heterocyclyl” refer to monocyclic, bicyclic, tricyclic, or polycyclic saturated, partially unsaturated, or aromatic ring systems having 3 to 20 total ring atoms and containing 1 to 4 heteroatoms in the case of monocyclics, 1 to 6 heteroatoms in the case of bicyclics, or 1 to 9 heteroatoms in the case of tricyclics or polycyclics. Exemplary heteroatoms include O, N, S, P, Si, and B. In some embodiments, for example, a heterocyclic ring contains 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, a heterocyclic ring contains 1, 2, or 3 (e.g., 1) heteroatoms selected from O, N, and S. In some embodiments, a heterocyclic ring contains one O atom. In some embodiments, a heterocyclic ring contains one S atom. In some embodiments, a heterocyclic ring contains one N atom. In some embodiments, for example, the heterocycle contains one, two, three, or four heteroatoms selected from O, N, and S. In some embodiments, the heterocycle contains one or two (e.g., one) heteroatoms selected from O, N, and S. In some embodiments, the heterocycle contains one O atom. In some embodiments, the heterocycle contains one S atom. In some embodiments, the heterocycle contains one N atom. The heterocyclic ring system may also contain one to three ring atoms that are -C(O)-, N-oxide, S-oxide, and / or S,S-dioxide groups, if valence is permitted. In some embodiments, the heterocyclyl is a heteroaryl as defined herein. Examples of heterocyclyl groups include the heteroaryl groups described herein, as well as fully and partially saturated groups, such as piperazinyl, pyrrolidinyl, pyrrolidonyl, pyrrolidonyl, tetrahydrothiophenyl 1,1-dioxide, thiomorpholinyl 1,1-dioxide, tetrahydrothiophenyl 1,1-dioxide, thiomorpholinyl 1,1-dioxide, dioxanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyridyl, dihydropyrazine, dihydropyridyl, dihydropyrrolyl, dihydrofuranyl, and dihydrothiophenyl. Heterocyclyl groups may include polycondensed and crosslinked rings.Non-limiting examples of condensed / crosslinked 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, 3-azabicyclo [3.2.1]octane, 2-oxabicyclo[1.1.0]butane, 2-oxabicyclo[2.1.0]pentane, 2-oxabicyclo[1.1.1]pentane, 3-oxabicyclo[3.1.0]hexane, 5-oxabicyclo[2.1.1]hexane, 3-oxabicyclo[3.2.0]heptane, 3-oxabicyclo[4.1.0]heptane, 7-oxabicyclo[2.2.1]heptane, 6-oxabicyclo[3.1.1]heptane, 7-oxabicyclo[4.2.0]octane, 2-oxabicyclo[2.2.2]octane, 3-oxabicyclo[3.2.1]octane, etc. Heterocyclyl groups may also include spirocyclic rings (e.g., spirocyclic dicyclic rings in which two rings are connected by only one atom).Non-restrictive examples of spirocyclic heterocyclines 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, 7-azaspiro[4.5]decane, 2,5-diazaspiro[3.6]decane, 3-azaspiro[5.5]undecane, and 2-oxaspiro[2. 2] These include pentane, 4-oxaspiro[2.5]octane, 1-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7-oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, 1,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, 1-oxaspiro[5.5]undecane, 3-oxaspiro[5.5]undecane, and 3-oxa-9-azaspiro[5.5]undecane.

[0050] The term "heteroaryl," as used herein, means a monocyclic, bicyclic, tricyclic, or polycyclic aromatic group (i.e., the entire ring system is aromatic) having 5 to 20 ring atoms, alternatively 5, 6, 9, 10, or 14 ring atoms, wherein at least one ring in the system contains one or more heteroatoms independently selected from the group consisting of O, N, S, P, Si, and B. In some embodiments, for example, the heteroaryl contains 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, the heteroaryl contains 1 or 2 (e.g., 1) heteroatoms selected from O, N, and S. In some embodiments, the heteroaryl contains 1 O atom. In some embodiments, the heteroaryl contains 1 S atom. In some embodiments, the heteroaryl contains 1 N atom. In some embodiments, for example, the heteroaryl contains 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, the heteroaryl comprises one or two heteroatoms (e.g., one) selected from O, N, and S. In some embodiments, the heteroaryl comprises one O atom. In some embodiments, the heteroaryl comprises one S atom. In some embodiments, the heteroaryl comprises one N atom. Examples of heteroaryls include thienyl, pyridinyl, furyl, oxazolyl, oxadiazolyl, pyrrolyl, imidazolyl, triazolyl, thiodiazolyl, pyrazolyl, isoxazolyl, thiadiazolyl, pyranyl, pyrazinyl, pyrimidinyl, pyridadinyl, triazinyl, thiazolylbenzothienyl, benzoxadiazolyl, benzofuranyl, benzimidazolyl, benzotriazolyl, cinolinyl, and indazolyl. This includes indolyl, isoquinolinyl, isothiazolyl, naphthilidinyl, 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]pyridinyl, pyrazolo[4,3-b]pyridinyl, tetrazolyl, and others.

[0051] The term "heterocycloalkyl" refers to a monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated ring system having 3 to 20 total ring atoms, and containing 1 to 3 heteroatoms in the case of a monocyclic, 1 to 6 heteroatoms in the case of a bicyclic, or 1 to 9 heteroatoms in the case of a tricyclic or polycyclic. Exemplary heteroatoms include O, N, S, P, Si, and B. In some embodiments, for example, the heterocycloalkyl contains 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, for example, the heterocycloalkyl contains 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, the heterocycloalkyl contains 1 or 2 (e.g., 1) heteroatoms selected from O, N, and S. In some embodiments, the heterocycloalkyl contains one O atom. In some embodiments, the heterocycloalkyl contains one S atom. In some embodiments, the heterocycloalkyl contains one N atom. Heterocycloalkyl ring systems may also contain 1 to 3 ring atoms that are -C(O)-, N-oxide, S-oxide, and / or S,S-dioxide groups, if valence is permitted. Examples of heterocycloalkyl groups include piperazinyl, pyrrolidinyl, pyrrolidonyl, tetrahydrothiophenyl 1,1-dioxide, thiomorpholinyl 1,1-dioxide, dioxanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyridyl, dihydropyrazine, dihydropyridyl, dihydropyrrolyl, dihydrofuranyl, and dihydrothiophenyl. Heterocycloalkyl groups may include polycondensed and crosslinked rings.Non-limiting examples of condensed / crosslinked 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, 3-azabicyclo [3.2.1]octane, 2-oxabicyclo[1.1.0]butane, 2-oxabicyclo[2.1.0]pentane, 2-oxabicyclo[1.1.1]pentane, 3-oxabicyclo[3.1.0]hexane, 5-oxabicyclo[2.1.1]hexane, 3-oxabicyclo[3.2.0]heptane, 3-oxabicyclo[4.1.0]heptane, 7-oxabicyclo[2.2.1]heptane, 6-oxabicyclo[3.1.1]heptane, 7-oxabicyclo[4.2.0]octane, 2-oxabicyclo[2.2.2]octane, 3-oxabicyclo[3.2.1]octane, etc. Heterocycloalkyl groups may also include spirocyclic rings (e.g., spirocyclic dicyclic rings in which two rings are connected by only one atom).Non-restrictive examples of spirocyclic heterocycloalkyls 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, 7-azaspiro[4.5]decane, 2,5-diazaspiro[3.6]decane, 3-azaspiro[5.5]undecane, and 2-oxaspiro[2 This includes .2]pentane, 4-oxaspiro[2.5]octane, 1-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7-oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, 1,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, 1-oxaspiro[5.5]undecane, 3-oxaspiro[5.5]undecane, 3-oxa-9-azaspiro[5.5]undecane, etc.

[0052] The term "heterocycloalkyl" refers to a monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated ring system having 3 to 20 total ring atoms, and containing 1 to 3 heteroatoms in the case of a monocyclic, 1 to 6 heteroatoms in the case of a bicyclic, or 1 to 9 heteroatoms in the case of a tricyclic or polycyclic. Exemplary heteroatoms include O, N, S, P, Si, and B. In some embodiments, for example, the heterocycloalkyl contains 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, for example, the heterocycloalkyl contains 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, the heterocycloalkyl contains 1 or 2 (e.g., 1) heteroatoms selected from O, N, and S. In some embodiments, the heterocycloalkyl contains one O atom. In some embodiments, the heterocycloalkyl contains one S atom. In some embodiments, the heterocycloalkyl contains one N atom. Heterocycloalkyl ring systems may also contain 1 to 3 ring atoms that are oxo, N-oxide, S-oxide, and / or S,S-dioxide groups, if valence is permitted. Examples of heterocycloalkyl groups include piperazinyl, pyrrolidinyl, pyrrolidonyl, tetrahydrothiophenyl 1,1-dioxide, thiomorpholinyl 1,1-dioxide, dioxanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyridyl, dihydropyrazine, dihydropyridyl, dihydropyrrolyl, dihydrofuranyl, and dihydrothiophenyl. Heterocycloalkyl groups may also contain polycondensed and crosslinked rings.Non-limiting examples of condensed / crosslinked 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, 3-azabicyclo [3.2.1]octane, 2-oxabicyclo[1.1.0]butane, 2-oxabicyclo[2.1.0]pentane, 2-oxabicyclo[1.1.1]pentane, 3-oxabicyclo[3.1.0]hexane, 5-oxabicyclo[2.1.1]hexane, 3-oxabicyclo[3.2.0]heptane, 3-oxabicyclo[4.1.0]heptane, 7-oxabicyclo[2.2.1]heptane, 6-oxabicyclo[3.1.1]heptane, 7-oxabicyclo[4.2.0]octane, 2-oxabicyclo[2.2.2]octane, 3-oxabicyclo[3.2.1]octane, etc. Heterocycloalkyl groups may also include spirocyclic rings (e.g., spirocyclic dicyclic rings in which two rings are connected by only one atom).Non-restrictive examples of spirocyclic heterocycloalkyls 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, 7-azaspiro[4.5]decane, 2,5-diazaspiro[3.6]decane, 3-azaspiro[5.5]undecane, and 2-oxaspiro[2 This includes .2]pentane, 4-oxaspiro[2.5]octane, 1-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7-oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, 1,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, 1-oxaspiro[5.5]undecane, 3-oxaspiro[5.5]undecane, 3-oxa-9-azaspiro[5.5]undecane, etc.

[0053] For the purpose of clarification, heteroaryls also include aromatic lactams, aromatic cyclic ureas, or their vinylogue analogs, where each ring nitrogen adjacent to the carbonyl is tertiary (i.e., all three valencies are occupied by non-hydrogen substituents), such as pyridone (e.g., [ka] ), pyrimidone (for example, [ka] ), pyridazinon (for example, [ka] ), pyrazinon (for example, [ka] ), and imidazolone (for example, [ka] ) contains one or more of the above, and each ring nitrogen adjacent to the carbonyl is tertiary (i.e., the oxo group (i.e., "=O") here is a component of the heteroaryl ring).

[0054] When used in this context, the term "saturated" refers only to single bonds present between constituent atoms.

[0055] As used herein, when a ring is described as “partially unsaturated,” it means that the aforementioned ring has one or more additional degrees of unsaturation (in addition to the degree of unsaturation attributable to the ring itself; for example, one or more double or triple bonds between the constituent ring atoms), but the ring is not aromatic. Examples of such rings include cyclopentene, cyclohexane, cycloheptene, dihydropyridine, tetrahydropyridine, dihydropyrrole, dihydrofuran, dihydrothiophene, and the like.

[0056] To avoid ambiguity and unless otherwise specified, for rings and cyclic groups (e.g., carbocyclic, aryl, cycloalkyl, heterocyclyl, heteroaryl, etc.) containing a sufficient number of ring atoms to form a bicyclic or higher-order cyclic system (e.g., tricyclic, polycyclic cyclic systems) as described herein, such rings and cyclic groups are those having a fused ring (where the condensation point is located on (i) adjacent ring atoms (e.g., [xx0] ring system (where 0 represents 0 atomic bridges) (e.g., [ka] )); (ii) Those existing in a single ring atom (spiro-fused ring systems) (for example, [ka] ), or (iii) those present in a continuous array of ring atoms (bridged ring systems where all bridge lengths > 0) (for example, [ka] It is understood that this includes (including).

[0057] Furthermore, any compound or structure provided herein is also intended to represent both an unlabeled and an isotope-labeled form of the compound. Compounds in these forms are referred to as “isotope-enriched.” An isotope-enriched compound has the structure described herein, except that one or more atoms are replaced by atoms having a selected atomic mass or mass number.

[0058] Examples of isotopes that may be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphoric acid, fluorine, chlorine, and iodine, for example, respectively. 2 H, 13 C, 14 C, 13 N, 15 N, 15 O, 17 O, 18 O, 31 P, 32 P, 35 S, 18 F, 36 C1, 123 I, and 125 I is an example. The compounds disclosed herein can be enriched with various isotopes, for example. 13 C and 14 Compounds incorporating radioactive isotopes such as 13C. Compounds enriched with such isotopes may be useful in metabolic studies, reaction kinetic studies, detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays, or in the radioactive treatment of patients.

[0059] As used herein, the term “isotope-enriched” includes “deuterated” compounds in which one or more hydrogen atoms are replaced by deuterium, such as a hydrogen atom on a carbon atom. Such compounds exhibit increased resistance to metabolism and are therefore useful in extending the half-life of any compound when administered to mammals, particularly humans. Such compounds are synthesized by means known in the art, for example, by using starting materials in which one or more hydrogen atoms are replaced by deuterium. In fact, the isotope-enriched compounds of this disclosure can generally be prepared by performing the procedures disclosed in the schemes or examples and preparations described below, by replacing readily available isotope-enriched reagents with non-isotope-enriched reagents.

[0060] The deuterium-enriched compounds of this disclosure may improve the DMPK (drug metabolism and pharmacokinetic) properties with respect to distribution, metabolism, and excretion (ADME). Substitution with heavier isotopes such as deuterium may result in certain therapeutic advantages due to higher metabolic stability (e.g., increased in vivo half-life or reduced dose requirements and / or improved therapeutic index compared to the corresponding non-enriched compound).

[0061] The concentration of heavier isotopes, such as deuterium, can be defined by isotopic enrichment factors. In some embodiments, the positions noted as "H" or "hydrogen" in the compounds described herein have hydrogen at their naturally occurring isotopic composition. In some embodiments, the positions noted as "H" or "hydrogen" in the compounds described herein have hydrogen enriched with deuterium above their naturally occurring isotopic composition; i.e., the compound is a deuterium-enriched compound. Examples of deuterium groups in the compounds described herein include deuteromethine. [ka] ), monotuteromethylene ( [ka] ) and diduteromethylene ( [ka] ), trideuteromethyl ( [ka] ), trideuteromethoxy( [ka] ) and others, but not limited to these. The compounds disclosed herein also include, [ka] This includes deuterium-enriched compounds at the alpha position of the oxo group, such as the following. The compounds of this disclosure also include, for example, [ka] This includes deuterium-enriched compounds adjacent to heteroatoms such as those mentioned above.

[0062] Furthermore, the compounds disclosed generally or specifically herein are intended to include all tautomer forms. Therefore, as an example, partial: [ka] Compounds containing: [ka] This includes tautomer forms containing [a specific compound]. Similarly, pyridinyl or pyrimidinyl moieties described as being optionally substituted by a hydroxyl group include pyridone or pyrimidone tautomer forms.

[0063] The compounds provided herein may encompass a variety of stereochemical forms. The compounds also include enantiomers (e.g., R and S isomers), diastereomers, and mixtures of enantiomers (e.g., R and S isomers), including racemic mixtures and mixtures of diastereomers, as well as individual enantiomers and diastereomers, resulting from structural asymmetry in a particular compound. Unless otherwise indicated, if a disclosed compound is named or illustrated by its structure without specifying its stereochemical structure (e.g., a "flat" structure) and has one or more chiral centers, it is understood that it represents all possible stereoisomers of the compound. Similarly, unless otherwise indicated, if a disclosed compound is named or illustrated by a structure that specifies its stereochemical structure (e.g., a structure with "wedge" and / or "dashed" bonds) and has one or more chiral centers, it is understood that it represents the indicated stereoisomers of the compound.

[0064] Details of one or more embodiments of this disclosure are described in the accompanying drawings and the following description. Other features and advantages of this disclosure will become apparent from the specification and claims. [Modes for carrying out the invention]

[0065] Bispecific tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a member of the bispecific tyrosine phosphorylation-regulated kinase (DYRK) family and also part of the larger CGMC kinase family. DYRK1A is a 763-amino acid, 85-kDa serine / threonine kinase located on chromosome 21. DYRK1A contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and 13 highly conserved consecutive histidine repeats. Alternative splicing of DYRK1A generates several transcript variants distinct from each other in either the 5' untranslated region or the 3' coding region, resulting in at least five distinct isoforms.

[0066] DYRK1A possesses catalytic activity regulated by autophosphorylation of the tyrosine residue (Y321), which results in constitutively activated serine / threonine kinase activity. Because DYRK1A is constitutively active, its activity is dose-dependent. Therefore, both elevated and decreased levels of DYRK1A (compared to wild-type levels) have been shown to cause neurological impairment.

[0067] DYRKIA exhibits a broad substrate spectrum (e.g., broad targets), including splicing factors, synaptic proteins, and transcription factors. It is universally expressed in all mammalian tissues and cells, but at varying levels, particularly high in fetal and adult brain tissue. The human DYRKIA gene is a candidate gene for treating several characteristics of Down syndrome, including intellectual disability and Alzheimer's disease, due to its localization in the Down syndrome-responsible region on chromosome 21 and its role in brain function. In particular, Drosophila with harmful mutations in the ortholog of DYRKIA ("Minibrain") have a reduced number of neurons in their central nervous system. Similarly, heterozygous mice with a disruption allele of the Dyrk1a gene exhibit reduced survival rate, behavioral changes, and growth retardation. Fotaki, et al., Mol Cell Biol., 22(18):6636-6647 (2014).

[0068] Identification of hundreds of genes lost control due to DYRK1A overexpression, as well as numerous cytoplasmic, cytoskeletal, and nuclear proteins, including transcription factors, that are phosphorylated by DYRK1A, demonstrates that DYRK1A overexpression is crucial for unrestricting multiple pathways in brain development and aging in individuals with Down syndrome. Identifying DYRK1A cell signaling or transmission pathways will provide a deeper understanding of how DYRK1A overexpression (or underexpression) leads to various disease conditions in which it is known to be involved. In particular, DYRK1A is known to be active in activated PI3K / Akt signaling, a pathway significantly involved in neuronal development, growth, and survival. DYRK1A is also known to be active in ASK1 / JNK1 activity, and inhibitors of DYRK1A may induce neuronal death and apoptosis. DYRK1A is also known to phosphorylate p53 during fetal brain development, and inhibitors of DYRK1A may prevent neuronal proliferative changes. DYRK1A also phosphorylates the synaptic proteins Amph1, Dynamin1, and Synaptojanin, which are involved in the regulation of endocytosis. Inhibitors of DYRK1A may preserve synaptic plasticity by preventing changes in the number, size, and morphology of dendritic spines. DYRK1A also phosphorylates and inhibits presenilin 1, a catalytic subunit of γ-secretase. Ryu, et al., J Neurochem., 115(3):574-84 (2010).

[0069] Overexpression of DYRK1A leads to structural and functional changes, including intellectual disability and dementia, such as Alzheimer's disease. In particular, genes involved in learning disabilities, altered synaptic flexibility, memory loss, and cell cycle abnormalities result in neuropathological symptoms similar to dementia associated with Alzheimer's disease. DYRK1A also affects the proliferation and differentiation of neuronal precursors, and therefore can influence neurogenesis and brain growth. It can also affect neurotransmission and dendritic spine formation through its interactions with synaptic proteins and the cytoskeleton.

[0070] One potential therapeutic source is DYRK1A inhibitors. Inhibitors that can normalize DYRK1A levels in Down syndrome may improve synaptic plasticity and delay the onset of Alzheimer's disease symptoms, including tau hyperphosphorylation. Therefore, inhibiting DYRK1A activity in individuals with Down syndrome may offset the phenotypic effects of its overexpression and could be a means of treating such developmental disorders, as well as preventing and / or mitigating age-related neurodegeneration, including Alzheimer's disease associated with Down syndrome. This study showed that inhibiting overexpressed DYRK1A resulted in normal DYRK1A levels and was found to improve cognitive and behavioral impairments in transgenic models. See, for example, Stringer, et al., Mol Genet Genomic Med, 5, 451-465 (2017) and Feki and Hibaoui, Brain Sci, 8, 187 (2018). However, despite the promising results, there is considerable variability in outcomes between studies. The differences stemmed from variations in the model, dosage, route of administration, inhibitor composition, and timing of administration.

[0071] Epigallocatechin gallate (EGCG) is the main flavonoid in green tea, and its therapeutic effects, including antioxidant, anti-inflammatory, anticancer, anti-infective, and neuroprotective properties, have been investigated. (See Bhat, et al. Towards the discovery of drug-like epigallocatechin gallate analogs as Hsp90 inhibitors, Bioorg Med Chem Lett, 24, 2263-2266 (2014)). EGCG is a non-ATP competitive DYRKlA inhibitor, and this study shows that a green tea extract containing 41% EGCG reduced cognitive decline observed in transgenic mice overexpressing DYRKlA. EGCG has also been shown to improve memory recognition and working memory. However, EGCG is not remarkably selective and has numerous off-target effects, which reduces its potential for long-term use.

[0072] SM07883 is an orally administered and bioavailable (%F 92% in mice, 109% in monkeys) BBB-permeable DYRK1A inhibitor (IC50 1.6 nM) that also exhibits potent inhibition of DYRK1B, CLK4, and GSK3β in kinase assays. It was found to prevent tau hyperphosphorylation in a mouse model. SM07883 was tested as a treatment for Alzheimer's disease in a Phase 1 trial in Australia (ACTRN12619000327189). However, according to the trial description page at www.anzctr.org.au, the last data collection date was May 2019, and the trial results have not been published.

[0073] This disclosure provides compounds of formula (I), (II), (III), (IV), (V), or (VI), or any of its subformulas, that inhibit bispecific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and pharmaceutically acceptable salts thereof. These chemical entities are useful, for example, to treat conditions, diseases, or disorders in a subject (e.g., humans) where increased (e.g., excessive) DYRK1A activation contributes to the pathology and / or symptoms and / or progression of neurological disorders. This disclosure also provides compositions containing the same, as well as methods for using and preparing them.

[0074] Compounds of formulas (I), (II), (III), and (IV) Some embodiments involve compounds of formula (I): [ka] or a pharmaceutically acceptable salt thereof (in the formula, each [ka] Y 1 , Y 2 , Y 3 , and Y 4 A bicyclic ring system containing ((i)Y 1 CR 3 Y 2N is Y 3 CR 4 Y 4 CR 3 (ii) Y 1 S is Y 2 C is Y 3 CR 4 or N and Y 4 CR 3 (iii) Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 Represent single or double bonds such that (this is the case); L is [ka] Selected from, * indicates a bond point to ring A, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes, Z' is -NR 1 -, -S(O)-, -S(O)2-, C 1-4 Alkylene, -NR 1 -C 1-4 Alkylene, -S(O)-C 1-4 Alkylene and -S(O)2-C 1-4 Selected from alkylenes; each C 1-4 Alkylenes may be optionally substituted with one or more halogens; Ring B is selected from (a), (b), and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); (b) [ka] (X 2 S and NR 7 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] (This represents single or double bonds such that ring B forms an aromatic bicyclic ring system.) However, ring B is (a) and Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 If is N, then p is 0; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl, C 1-4 -C(O)C optionally substituted with haloalkyl and one or more halogens. 3-6 Selected from cycloalkyl groups; R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R 10 ) Selected from NO2 and -CN; R 3 and R 4 These are, independently, hydrogen, halogen, and C in their respective existences. 1-4 Alkyl and C 1-4 Selected from haloalkyl; R A is halogen, C 1-4Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 , -CN, -S(O)2C 1-4 Alkyl, C 3-6 Cycloalkyl, and 3- to 6-membered heterocycloalkyl, provided that Y 1 is CR 3 and Y 2 is N and Y 4 is CR 3 or when Y 1 is CR 3 and Y 2 is N and Y 4 is N, then R A is further selected from -OR 11 ; Y 1 is CR 3 and Y 2 is N and Y 3 is CH, ring B is (a), p is 0, X 1 is N, and ring A is 1-fluoro-1-tetrahydropyranyl, then R A is further selected from hydrogen; Y 1 is S, Y 2 is C, and X 1 is N, then R A is further selected from hydrogen; Ring A is Cyclopropyl substituted with one or more C 1-6 alkyl or -CN, a carbocyclic ring substituted with one or more halogens, a 3- to 6-membered heterocyclic ring substituted with one or more halogens, C 3-6 spirocyclic carbocyclic ring, and a 5- to 6-membered spirocyclic heterocyclic ring (any of these may be C 5-6 alkyl, C 1-6 haloalkyl, -OR 1-6 , -SR 12 , -N(R 12 )2, -C(O)R 12 )2, -C(O)R12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle); C 7-12 Carbon rings and 7-12 membered heterocycles (each of these being halogens, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4Optionally substituted with one or more substituents independently selected from 3- to 6-membered heterocycles optionally substituted with alkyl, provided that when ring B is selected from (b), then ring A is not chroman) selected from; provided that when one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then ring A is C 4-6 further selected from carbocycles and 3- to 6-membered heterocycles, each of which is C 1-6 alkyl, C 1-6 haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 , -S(O)2R 12 , -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 , -NO2, =O, -CN, and optionally substituted with one or more substituents independently selected from 3- to 6-membered heterocycles optionally substituted with alkyl: (i) Ring B is (a), and R A is selected from halogen, C 1-4 haloalkyl, C 3-6 cycloalkyl, -NR 11 , and -OR 11 selected from;<0006-08>(ii) Y 1 is S, Y 2 is C, ring B is (a), and X 1 ​​is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (vi) Ring B is (c); and (vii)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 is N; (viii)Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 And ring B is (a) or (c); However, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl; R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -N(R 13 )S(O)2(R 13), -S(O)2R 13 -S(O)2N(R 13 ) Selected from -NO2 and -CN, however, R A ga-OR 11 If that is the case, then R 5 is -OR 13 Not; R 6 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14 -S(O)2N(R 14 )2, -NO2, =O, and -CN are selected; R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14 -S(O)2N(R 14 )2, -NO2, =O, and -CN are selected; R 7 and R 9 These are, independently, hydrogen and C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups; m is selected from 0 and 1; p is selected from 0, 1, and 2; q is selected from 0, 1, and 2; (r is selected from 0, 1, and 2) To provide.

[0075] In some embodiments, if a site or list of sites is optionally replaced by one or more substituents, then one or more substituents are 1 to 4 substituents (e.g., 1 to 3, 2 to 4, 2 to 3, 1 to 2, 3 to 4, 1, 2, 3, or 4 substituents). For example, one or more substituents are 1 to 4 substituents. For example, one or more substituents are 1 substituent.

[0076] In some embodiments, for a compound of formula (I), Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 CR 3 Or N. In some embodiments, Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 In some embodiments, Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 CR 3 In some embodiments, Y 1 S is Y2 C is Y 3 CR 4 or N and Y 4 CR 3 In some embodiments, Y 1 S is Y 2 C is Y 3 CR 4 Y 4 CR 3 In some embodiments, Y 1 S is Y 2 C is Y 3 N is Y 4 CR 3 In some embodiments, Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 That is the case.

[0077] In some embodiments, for a compound of formula (I), Y 1 CH is Y 2 N is Y 3 CH is Y 4 is CH or N. In some embodiments, Y 1 CH is Y 2 N is Y 3 CH is Y 4 In some embodiments, Y 1 CH is Y 2 N is Y 3 CH is Y 4 CH is. In some embodiments, Y 1 S is Y 2 C is Y 3 is CH or N, Y 4 CH is. In some embodiments, Y 1 S is Y 2 C is Y 3 CH is Y 4CH is. In some embodiments, Y 1 S is Y 2 C is Y 3 N is Y 4 CH is. In some embodiments, Y 1 N is Y 2 N is Y 3 CH is Y 4 It is CH.

[0078] In some embodiments, the compound is of formula (IA): [ka] or a pharmaceutically acceptable salt thereof; (wherein Y 3 is CH or N, Y 4 (is CH or N). In some embodiments, Y 3 CH is Y 4 It is CH.

[0079] In some embodiments, the compound is of formula (IB): [ka] or a pharmaceutically acceptable salt thereof; the compound is of the formula (IC) (wherein Y 3 is CH or N, Y 4 (It is CH or N) [ka] or a pharmaceutically acceptable salt thereof (wherein Y 3 (is CH or N).

[0080] In some embodiments, the compound is of formula (ID): [ka] or a pharmaceutically acceptable salt thereof (wherein Y 4 (is CH or N).

[0081] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), L is [ka] Not necessarily. In some embodiments, L is [ka] Not necessarily. In some embodiments, L is [ka] But no.

[0082] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes, each C 1-4 The alkylene is optionally substituted with one or more halogens. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes, each C 1-4 Alkylenes are optionally substituted with one or more halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes, each C 1-4 Alkylenes are optionally substituted with one or more halogens; R 1Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes, each C 1-4 Alkylenes are optionally substituted with one or more halogens; each R 1 is hydrogen. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes; each R 1 It is hydrogen.

[0083] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylenes, each C 1-2 Alkylenes are optionally substituted with one or more halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylenes, each C 1-2 Alkylenes are optionally substituted with one or more halogens; each R 1 is hydrogen. In some embodiments, Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylenes; each R1 It is hydrogen.

[0084] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), Z' is -NR 1 -, -S(O)-, -S(O)2-, C 1-4 Alkylene, -NR 1 -C 1-4 Alkylene, -S(O)-C 1-4 Alkylene and -S(O)2-C 1-4 Selected from alkylenes; each C 1-4 Alkylenes are optionally substituted with one or more halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, Z' is -NR 1 -, -S(O)-, -S(O)2-, C 1-4 Alkylene, -NR 1 -C 1-4 Alkylene, -S(O)-C 1-4 Alkylene and -S(O)2-C 1-4 Selected from alkylenes; each R 1 It is hydrogen.

[0085] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), Z' is -S(O)2-, C 1-4 Alkylene and -S(O)2-C 1-4 Selected from alkylenes; each C 1-4 The alkylene is optionally substituted with one or more halogens. In some embodiments, Z' is -S(O)2-, C 1-4 Alkylene and -S(O)2-C 1-4 Selected from alkylenes. In some embodiments, Z' is optionally substituted with one or more halogens. 1-4 It is an alkylene. In some embodiments, Z' is C 1-4 It is an alkylene. In some embodiments, Z' is a C optionally substituted with one or more halogens. 1-4 It is alkylene; R 1is hydrogen. In some embodiments, Z' is C 1-4 It is alkylene; R 1 It is hydrogen.

[0086] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), Z' is -NR 1 -, -S(O)-, -S(O)2-, C 1-2 Alkylene, -NR 1 -C 1-2 Alkylene, -S(O)-C 1-2 Alkylene and -S(O)2-C 1-2 Selected from alkylenes; each C 1-2 Alkylenes are optionally substituted with one or more halogens; each R 1 is hydrogen. In some embodiments, Z' is -S(O)2-, C 1-2 Alkylene and -S(O)2-C 1-2 Selected from alkylenes; each C 1-2 Alkylene is optionally substituted with one or more halogens, R 1 is hydrogen. In some embodiments, Z' is C, which is optionally substituted with one or more halogens. 1-2 It is an alkylene. In some embodiments, Z' is C 1-2 It is an alkylene. In some embodiments, Z' is a C optionally substituted with one or more halogens. 1-2 It is alkylene; R 1 is hydrogen. In some embodiments, Z' is C 1-2 It is alkylene; R 1 It is hydrogen.

[0087] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes; Z' is -S(O)2-, C 1-4 Alkylene and -S(O)2-C1-4 Selected from alkylenes; each C 1-4 Alkylenes are optionally substituted with one or more halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylene; Z' is -NR 1 -, -S(O)-, -S(O)2-, C 1-4 Alkylene, -NR 1 -C 1-2 Alkylene, -S(O)-C 1-4 Alkylene and -S(O)2-C 1-4 Selected from alkylenes, each C 1-4 The alkylene is optionally substituted with one or more halogens. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylene; Z' is -NR 1 -, -S(O)-, -S(O)2-, C 1-4 Alkylene, -NR 1 -C 1-4 Alkylene, -S(O)-C 1-4 Alkylene and -S(O)2-C 1-4 Selected from alkylenes, each C 1-4 Alkylenes are optionally substituted with one or more halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4Selected from alkylenes; in some embodiments, Z' is -S(O)2-, C 1-4 Alkylene and -S(O)2-C 1-4 Selected from alkylenes; each C 1-4 Alkylenes are optionally substituted with one or more halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes; Z' is C, optionally substituted with one or more halogens. 1-4 Alkylene; each C 1-4 Alkylenes are optionally substituted with one or more halogens; each R 1 is hydrogen. In some embodiments, Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylene; Z' is C 1-4 It is alkylene; each R 1 It is hydrogen.

[0088] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylene; Z' is -NR 1 -, -S(O)-, -S(O)2-, C 1-2 Alkylene, -NR 1 -C 1-2 Alkylene, -S(O)-C 1-2 Alkylene and -S(O)2-C 1-2 Selected from alkylenes, each C 1-2 Alkylenes are optionally substituted with one or more halogens; R1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylenes; in some embodiments, Z' is -S(O)2-, C 1-2 Alkylene and -S(O)2-C 1-2 Selected from alkylenes; each C 1-2 Alkylenes are optionally substituted with one or more halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylenes; Z' is C, optionally substituted with one or more halogens. 1-2 Alkylene; each C 1-2 Alkylenes are optionally substituted with one or more halogens; each R 1 is hydrogen. In some embodiments, Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylene; Z' is C 1-4 It is alkylene; each R 1 is hydrogen. In some embodiments, Z is selected from -O-, -NH-, -CH2-, -O-CH2-, and -NH-CH2-; Z' is -CH2-.

[0089] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), L is [ka] Selected from.

[0090] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), L is [ka] In some embodiments, L is [ka] And; Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes, each C 1-4 Alkylenes are optionally substituted with 1-2 halogens; 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, L is [ka] And; Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes, each C 1-4 Alkylenes are optionally substituted with 1-2 halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, L is [ka] And; Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylene; R1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, L is [ka] And; Z is -O-, -NR 1 -, C 1-4 Alkylene, -OC 1-4 Alkylene and -NR 1 -C 1-4 Selected from alkylenes; each R 1 is hydrogen. In some embodiments, L is [ka] And; Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylenes, each C 1-2 Alkylenes are optionally substituted with 1-2 halogens; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, L is [ka] And; Z is -O-, -NR 1 -, C 1-2 Alkylene, -OC 1-2 Alkylene and -NR 1 -C 1-2 Selected from alkylenes, each C 1-2 Alkylenes are optionally substituted with 1-2 halogens; each R 1 is hydrogen. In some embodiments, L is [ka] Selected from.

[0091] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), L is [ka] In some embodiments, L is [ka] And Z' is C, which is optionally substituted with 1-2 halogens. 1-4 Selected from alkylene; R 1 is hydrogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, L is [ka] And Z' is C, which is optionally substituted with 1-2 halogens. 1-4 Selected from alkylene; R 1 is hydrogen. In some embodiments, L is [ka] And; Z' is C 1-4 Selected from alkylene; R 1 is hydrogen. In some embodiments, L is [ka] That is the case.

[0092] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), or (ID), L is [ka] In some embodiments, L is [ka] And; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, L is [ka] And; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl, C 1-4 Selected from haloalkyls. In some embodiments, L is [ka] And; R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, L is [ka] Selected from. In some embodiments, L is [ka] That is the case.

[0093] Some embodiments involve compounds of formula (II): [ka] or a pharmaceutically acceptable salt thereof (in the formula, each [ka] Y 1 , Y 2 , and Y 3 A bicyclic ring system containing ((i)Y 1 CR 3 Y 2 (ii) Y 1 S is Y 2 This represents a single or double bond such that (C) is the case; Y 3 N and CR 4 Selected from; Ring B is selected from (a), (b), and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); (b) [ka] (X 2 S and NR 7 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] This represents single or double bonds such that ring B forms an aromatic bicyclic ring system. R 1 is hydrogen, C 1-4 -C(O)C optionally substituted with alkyl and one or more halogens. 3-6 Selected from cycloalkyl groups; R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R 10 ) Selected from NO2 and -CN; R 3 and R 4 These are, independently, hydrogen, halogen, and C. 1-4 Alkyl and C 1-4 Selected from haloalkyl; RA is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 -CN, -S(O)2C 1-4 Alkyl, C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl groups, however, Y 1 CR 3 Y 2 If it is N, then R A is -OR 11 Further selections are made from these. Y 1 CR 3 Y 2 N is Y 3 is CH, ring B is (a), p is 0, X 1 If is N and ring A is 1-fluoro-1-tetrahydropyranyl, then R A It is further selected from hydrogen, Y 1 S is Y 2 C is X 1 If it is N, then R A It is further selected from hydrogen; Ring A is, C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of which is substituted with one or more halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12, -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle); C 7-12 Carbon rings and 7-12 membered heterocycles (each of these being halogens, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle, provided that if ring B is selected from (b), then ring A is not chroman. Selected from; However, if one or more of (i), (ii), (ii), (iv), and (v) apply, then ring A is C 4-6Further selections are made from carbon rings and 3- to 6-membered heterocycles, each of which is C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles: (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4It is alkyl; and (vi) Ring B is (c); However, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl; R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -N(R 13 )S(O)2(R 13 ), -S(O)2R 13 -S(O)2N(R 13 ) Selected from -NO2 and -CN, however, R A ga-OR 11 If that is the case, then R 5 is -OR 13 Not; R 6 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14 -S(O)2N(R 14)2, -NO2, =O, and -CN are selected; R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14 -S(O)2N(R 14 )2, -NO2, =O, and -CN are selected; R 7 and R 9 These are, independently, hydrogen and C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups; m is selected from 0, 1, and 2; p is selected from 0, 1, and 2; q is selected from 0, 1, and 2; (r is selected from 0, 1, and 2) To provide.

[0094] In some embodiments of the compound of formula (II), Y 1 CR 3 Y 2 is N; Y 3 In some embodiments, Y 1 CR 3Y 2 is N; Y 3 CR 4 In some embodiments, Y 1 CR 3 Y 2 is N; Y 3 CH is. In some embodiments, Y 1 CR 3 Y 2 N is Y 4 CR 3 In some embodiments, Y 1 CR 3 Y 2 is N; Y 3 is N; ring B is (a). In some embodiments, Y 1 CR 3 So; Y 2 is N; Y 3 CR 4 And; ring B is (a). In some embodiments, Y 1 , S de ri, Y 2 C is C. In some embodiments, Y 1 S is Y 2 C is; Y 3 In some embodiments, Y 1 S is Y 2 C is; Y 3 CR 4 In some embodiments, Y 1 S is Y 2 C is; Y 3 CH is. In some embodiments, Y 3 In some embodiments, Y 3 CR 4 And; R 4 Y is selected from hydrogen and halogen. In some embodiments, Y 3 CH is. In some embodiments, Y 1 S is Y 2 C is X 1 In some embodiments, Y1 S is Y 2 C is; R A C 1-4 Selected from alkyl groups. In some embodiments, Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 In some embodiments, Y 1 CR 3 Y 2 N is Y 3 CH is Y 4 In some embodiments, Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 In some embodiments, Y 1 CH is Y 2 N is Y 3 CR 4 Y 4 is N; R 4 These are hydrogen, halogens, and C 1-4 Selected from alkyl groups.

[0095] In some embodiments, the compound is of formula (IIA): [ka] or a pharmaceutically acceptable salt thereof (wherein Y 3 is CH or N, Y 4 (is CH or N).

[0096] In some embodiments, the compound is of formula (IIA-1): [ka] or a pharmaceutically acceptable salt thereof (wherein Y 3 (is CH or N).

[0097] In some embodiments, the compound is of formula (IIB): [ka] or a pharmaceutically acceptable salt thereof (wherein Y 3 is CH or N, Y 4 (is CH or N). In some embodiments, R 3 These are hydrogen, halogens, and C 1-4 Selected from alkyl groups.

[0098] In some embodiments, the compound is of formula (IIB-1): [ka] or a pharmaceutically acceptable salt thereof (wherein Y 3 (is CH or N). In some embodiments, R 3 These are hydrogen, halogens, and C 1-4 Selected from alkyl groups.

[0099] In some embodiments, the compound is of formula (IIC): [ka] or a pharmaceutically acceptable salt thereof (wherein Y 3 (is CH or N).

[0100] In some embodiments, the compound is of formula (IIC-1): [ka] or a pharmaceutically acceptable salt thereof.

[0101] In some embodiments, the compound is of formula (IID). [ka] or a pharmaceutically acceptable salt thereof (wherein Y 4 (is CH or N).

[0102] In some embodiments, the compound is of formula (IID-1): [ka] or a pharmaceutically acceptable salt thereof.

[0103] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), each R 3 These are hydrogen, halogens, and C 1-4 Selected from alkyl groups. In some embodiments, each R 3 R is selected from hydrogen and halogens. In some embodiments, 3 is hydrogen. In some embodiments, R 3 is a halogen. In some embodiments, R 3 is fluoro. In some embodiments, R 3 is chloro. In some embodiments, R 3 C 1-4 It is alkyl. In some embodiments, R 3 is methyl. In some embodiments, R 3 C 1-4 In some embodiments, R 3 It is trifluoromethyl.

[0104] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4Selected from haloalkyls. In some embodiments, R 1 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. 1 Independently, in each of their forms, hydrogen, -CH3, -CF3, -CH2CH3, [ka] Selected from.

[0105] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), R 1 These are hydrogen, -CH3, -CH2CH3, [ka] Selected from. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 C 1-4 It is alkyl. In some embodiments, R 1 -C(O)C, which is optionally substituted with one or more halogens. 3-6 It is cycloalkyl. In some embodiments, R 1 -C(O)C substituted with one or more fluoropolymers 3-6 It is cycloalkyl. In some embodiments, R 1 is -CH3. In some embodiments, R 1 is -CH2CH3. In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, each R 1It is hydrogen.

[0106] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), R 2 Independently, halogens and C in each presence 1-4 Selected from alkyl groups. In some embodiments, R 2 is a halogen. In some embodiments, R 2 C 1-4 It is alkyl. In some embodiments, R 2 C 1-4 In some embodiments, R 2 is -OR 10 In some embodiments, R 2 -SR 10 In some embodiments, R 2 is -N(R 10 )2. In some embodiments, R 2 It is NO2. In some embodiments, R 2 is -CN. In some embodiments, R 2 Independently, in each existence, C 1-4 Selected from alkyl groups.

[0107] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), m is 0 or 1. In some embodiments, m is 1 or 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2.

[0108] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), R 3 and R 4 These are, independently, hydrogen, halogen, and C in their respective existences. 1-4 Selected from alkyl groups. In some embodiments, R 3 and R 4 Each is independently selected from hydrogen and halogen in each presence. In some embodiments, R 3 and R 4 These are, independently, hydrogen and C in their respective existences. 1-4 Selected from alkyl groups. In some embodiments, each R 3 is hydrogen. In some embodiments, each R 4 It is hydrogen.

[0109] In some embodiments, the compound is of formula (IIA-2): [ka] or a pharmaceutically acceptable salt thereof.

[0110] In some embodiments, the compound is of formula (IIB-2): [ka] or a pharmaceutically acceptable salt thereof.

[0111] In some embodiments, the compound is of formula (IIC-2): [ka] or a pharmaceutically acceptable salt thereof.

[0112] In some embodiments, the compound is of formula (IID-2): [ka] or a pharmaceutically acceptable salt thereof.

[0113] In some embodiments, the compound is of formula (IIE-2): [ka] or a pharmaceutically acceptable salt thereof.

[0114] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is selected from (a), (b), and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); (b) [ka] (X 2 S and NR 7 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] (This represents single or double bonds such that ring B forms an aromatic bicyclic ring system.) However, ring B is (a) and Y 1 CR 3 Y 2 N is Y 3 R 4 Y 4 If p is N, then p is 0.

[0115] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is selected from (a) and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] The single or double bonds represent ring B such that it forms an aromatic bicyclic ring system.

[0116] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (b) [ka] Selected from, X 2 S and NR 7 Selected from.

[0117] In some embodiments, ring B is (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] (This represents single or double bonds such that ring B forms an aromatic bicyclic ring system.) Selected from, However, ring B is (a) and Y 1 CR 3 Y 2 N is Y 3 R 4 Y 4 If p is N, then p is 0.

[0118] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is selected from (a) and (c): (a) [ka] (X 1 is selected from N, CH, and CH); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from each [ka] (This represents a single or double bond such that ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan.) R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3- to 6-membered heterocycloalkyl groups; Y 1 CR 3 Y 2 If it is N, then R A is -OR 11 Further selection from; R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl groups; R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Selected from haloalkyl and -CN; R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Selected from haloalkyl and -CN; R 9 is hydrogen and C 1-4 Selected from alkyl groups; p is selected from 0 and 1; r is selected from 0 and 1.

[0119] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is selected from (a) and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from each [ka] (This represents a single or double bond such that ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan.) R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from; Y 1 CR 3 Y 2 If it is N, then R A These are -OH, -OCH3, and [ka] Further selections from; R 5 In each instance, it is selected from -F, -Cl, and -CH3; R 9 It is selected from hydrogen and -CH3; p is selected from 0 and 1; r is 0.

[0120] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (a) [ka] Selected from, X 1 These are N, CH, and CR 5 Selected from; however, Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 If is N, then p is 0, and in some embodiments, X 1 This is selected from N and CH. In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0121] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 -CN, -S(O)2C 1-4 Alkyl, C 3-6Selected from cycloalkyl and 3-6 member heterocycloalkyl groups, however, Y 1 CR 3 Y 2 N is Y 4 CR 3 If Y 1 CR 3 Y 2 N is Y 4 If it is N, then R A is -OR 11 Further selections are made from these. Y 1 CR 3 Y 2 N is Y 3 is CH, ring B is (a), p is 0, X 1 If is N and ring A is 1-fluoro-1-tetrahydropyranyl, then R A It is further selected from hydrogen, Y 1 S is Y 2 C is X 1 If it is N, then R A It is further selected from hydrogen.

[0122] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 -CN, -S(O)2C 1-4 Alkyl, C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl groups, however, Y 1CR 3 Y 2 N is Y 4 CR 3 If Y 1 CR 3 Y 2 N is Y 4 If it is N, then R A is -OR 11 Further selections from; R 11 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl, C 1-4 Haloalkyl; and C 3-6 Selected from cycloalkyl groups.

[0123] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-5 Selected from cycloalkyl and 5-6 member heterocycloalkyl groups, however, Y 1 CR 3 Y 2 N is Y 4 CR 3 If Y 1 CR 3 Y 2 N is Y 4 If it is N, then R A is -OR 11 Further selections from; R 11 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl, C1-4 Haloalkyl and C 3-6 Selected from cycloalkyl groups.

[0124] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3- to 6-membered heterocycloalkyl groups; Y 1 CR 3 Y 2 N is Y 4 CR 3 is, or Y 1 CR 3 Y 2 N is Y 4 If it is N, then R A is -OR 11 Further selection from; R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3- to 6-membered heterocycloalkyl groups; Y 1 CR 3 Y2 If it is N, then R A is -OR 11 Further selection from; R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl groups.

[0125] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R A is a halogen. In some embodiments, R A C 1-4 It is alkyl. In some embodiments, R A is methyl. In some embodiments, R A is ethyl. In some embodiments, R A C 1-4 In some embodiments, R A C 1-4 It is a hydroxyalkyl group. In some embodiments, R A is -N(R 11 )2. In some embodiments, R A -SR 11 In some embodiments, R A is -N(R 11 )C(O)R 11 In some embodiments, R A is -CN. In some embodiments, R A C 3-6 It is cycloalkyl. In some embodiments, R A These are 3- to 6-membered heterocycloalkyl groups.

[0126] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Y 1 CR 3 Y 2 is N; R A is -OR 11 Further selections are made from R A ga-OR 11 If that is the case, then R 5 is -OR 13 No. In some embodiments, Y 1 CR 3 Y 2 N is Y 4 N is R A is -OR 11 Further selection from. In some embodiments, Y 1 CR 3 Y 2 N is Y 3 is CH, ring B is (a), p is 0, X 1 is N, and ring A is 1-fluoro-1-tetrahydropyranyl; R A is further selected from hydrogen. In some embodiments, Y 1 S is Y 2 C is X 1 is N; R A It is further selected from hydrogen.

[0127] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from; Y 1 CR 3 Y 2 If it is N, then R A These are -OH, -OCH3, and [ka] Further selection from. In some embodiments, R A is -F. In some embodiments, R A is -Cl. In some embodiments, R A is -CN. In some embodiments, R A is -NH2. In some embodiments, R A is -OH. In some embodiments, R A is -OCH3. In some embodiments, R A teeth, [ka] In some embodiments, R A is -CH3. In some embodiments, R A is -CF3. In some embodiments, R A is -CHF2. In some embodiments, R A teeth, [ka] In some embodiments, R A teeth, [ka] In some embodiments, R A teeth, [ka] In some embodiments, R A teeth, [ka] In some embodiments, R A teeth, [ka] That is the case.

[0128] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2.

[0129] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)OR 13 ,-C(O)N(R 13 ) Selected from -NO2 and -CN, however, R A ga-OR 11 If that is the case, then R 5 is -OR 13 Instead; R 13 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4Alkyl, C 1-4 Haloalkyl, -SR 13 , -N(R 13 )2, -C(O)OR 13 ,-C(O)N(R 13 ) Selected from -NO2 and -CN; R 13 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -N(R 13 )2, and -CN are selected, however, R A ga-OR 11 If that is the case, then R 5 is -OR 13 Instead; R 13 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -N(R) 13 )2, and selected from -CN;R 13 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl and -OR 13 Selected from, however, R A ga-OR 11 If that is the case, then R 5 is -OR 13 Instead; R 13 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl and C 1-4Selected from haloalkyls. In some embodiments, R 5 R is independently selected from halogens in each presence. In some embodiments, R 5 Independently, in each existence, C 1-4 Selected from alkyl groups. In some embodiments, R 5 Independently, in each existence, C 1-4 Selected from haloalkyl groups.

[0130] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R 13 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 13 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, each R 13 It is hydrogen.

[0131] In some embodiments, or in compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (b) [ka] Selected from, X 2 S and NR 7 Selected from.

[0132] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), X 2 In some embodiments, X 2 , NR 7 In some embodiments, X 2 is S or NH. In some embodiments, X 2 is NH. In some embodiments, X 2 In some embodiments, R 7 is hydrogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 7 is hydrogen, and C 1-4 Selected from alkyl groups.

[0133] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), q is 0 or 1. In some embodiments, q is 1. In some embodiments, q is 0. In some embodiments, q is 1 or 2. In some embodiments, q is 2.

[0134] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R 6 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR14 , -N(R 14 )2, -C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14 -S(O)2N(R 14 ) Selected from -NO2 and -CN; R 14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 6 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)OR 14 -S(O)2N(R 14 ) Selected from -NO2 and -CN; R 14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 6 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, and selected from -CN;R 14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 6 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , and -N(R 14 ) Selected from 2, R 14 Independently, hydrogen and C exist in each of their respective forms.1-4 Selected from alkyl groups. In some embodiments, R 6 Independently, in each presence, halogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 6 Independently, halogens and C in each presence 1-4 Selected from alkyl groups. In some embodiments, R 6 R is independently selected from halogens in each presence. In some embodiments, R 6 Independently, in each existence, C 1-4 Selected from alkyl groups.

[0135] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R 6 is a halogen. In some embodiments, R 6 C 1-4 It is alkyl. In some embodiments, R 6 C 1-4 In some embodiments, R 6 is -OR 14 In some embodiments, R 6 -SR 14 In some embodiments, R 6 is -N(R 14 )2. In some embodiments, R 6 is -C(O)R 14 In some embodiments, R 6 is -C(O)OR 14 In some embodiments, R 6 is -OC(O)R 14 In some embodiments, R 6 is -C(O)N(R 14 )2. In some embodiments, R 6 is -N(R14 )C(O)R 14 In some embodiments, R 6 is -N(R 14 )S(O)2(R 14 ) is. In some embodiments, R 6 is -S(O)2R 14 In some embodiments, R 6 is -S(O)2N(R 14 )2. In some embodiments, R 6 is -NO2. In some embodiments, R 6 In some embodiments, R 6 It is -CN.

[0136] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from each [ka] Ring B is selected from single or double bonds such that it forms an aromatic bicyclic ring system. In some embodiments, ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan;

[0137] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] The ring B is a single or double bond such that it forms an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan. In some embodiments, ring B is an aromatic bicyclic ring system selected from benzothiazole and benzofurazan. In some embodiments, ring B is an aromatic bicyclic ring system selected from benzothiazole and benzimidazole. Ring B is an aromatic bicyclic ring system selected from benzimidazole and benzofurazan. In some embodiments, ring B is benzothiazole. In some embodiments, ring B is benzimidazole. In some embodiments, ring B is benzofurazan.

[0138] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), X 3 In some embodiments, X 3 In some embodiments, X 3 is NH. In some embodiments, X 4 In some embodiments, X 4 CR 9 In some embodiments, X3 S is X 4 In some embodiments, X 3 S is X 4 CR 9 In some embodiments, X 3 is N and X 4 In some embodiments, X 3 N is X 4 CR 9 In some embodiments, X 3 NH and X 4 In some embodiments, X 3 NH and X 4 CR 9 That is the case.

[0139] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), r is 0 or 1. In some embodiments, r is 1. In some embodiments, r is 0. In some embodiments, r is 1 or 2. In some embodiments, r is 2.

[0140] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14 -S(O)2N(R 14 ) Selected from -NO2 and -CN; R 14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)OR 14 ,-C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -N(R 14 )S(O)2(R 14 ), -S(O)2R 14 -S(O)2N(R 14 ) Selected from -NO2 and -CN; R 14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, and selected from -CN;R 14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 8 Independently, in each presence, halogen, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 )2, and selected from -CN;R14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , and -N(R 14 ) Selected from 2; R 14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 8 Independently, in each presence, halogen, C 1-4 Haloalkyl, -OR 14 , and -N(R 14 ) Selected from 2, R 14 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 8 Independently, in each presence, halogen, C 2-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 8 Independently, halogens and C in each presence 1-4 Selected from haloalkyls. In some embodiments, R 8 R is independently selected from halogens in each presence. In some embodiments, R 8 Independently, in each existence, C 2-4 Selected from alkyl groups. In some embodiments, R 8 Independently, in each existence, C 1-4 Selected from haloalkyls. In some embodiments, R 8 It is not methyl.

[0141] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R 9 is hydrogen, C1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 9 is hydrogen, and C 1-4 Selected from alkyl groups. In some embodiments, R 9 is hydrogen. In some embodiments, R 9 C 1-4 It is alkyl. In some embodiments, R 9 is methyl. In some embodiments, R 9 It is hydrogen.

[0142] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R 5 Independently, halogens and C in each presence 1-4 Selected from alkyl groups. In some embodiments, R 6 and R 8 These are, independently, halogens and C in their respective presences. 1-4 Selected from alkyl groups. In some embodiments, R 7 and R 9 These are hydrogen and C, respectively. 1-4 It is selected independently of alkyl.

[0143] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is selected from (a) and (c): (a) [ka] (X 1 These are N, CH, and CR 5Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from each [ka] (This represents a single or double bond such that ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan.) R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from; Y 1 CR 3 Y 2 If it is N, then R A These are -OH, -OCH3, and [ka] Further selections from; R 5 In each instance, it is selected from -F, -Cl, and -CH3; R 9 It is selected from hydrogen and -CH3; p is selected from 0 and 1; r is 0; however, ring B is (a) and Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 If p is N, then p is 0.

[0144] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is selected from (a) and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from each [ka] (This represents a single or double bond such that ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan.) R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from; Y 1 CR 3 Y 2 If it is N, then R A These are -OH, -OCH3, and [ka] Further selections from; R 5 In each instance, it is selected from -F, -Cl, and -CH3; R 9 It is selected from hydrogen and -CH3; p is selected from 0 and 1; r is 0; however, ring B is (a) and Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 If p is N, then p is 0.

[0145] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is selected from (a) and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from each [ka] (This represents a single or double bond such that ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan.) R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from; Y 1 CR 3 Y 2If it is N, then R A These are -OH, -OCH3, and [ka] Further selections from; R 5 In each instance, it is selected from -F, -Cl, and -CH3; R 9 It is selected from hydrogen and -CH3; p is selected from 0 and 1; r is 0; however, ring B is (a) and Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 If p is N, then p is 0.

[0146] In some embodiments, Y 1 CR 3 Y 2 N is R A is -OH. In some embodiments, Y 1 CR 3 Y 2 N is R A is -OCH3. In some embodiments, Y 1 CR 3 Y 2 N is R A teeth, [ka] In some embodiments, R A ga-OR 11 If that is the case, then R 5 is -OR 13 isn't it.

[0147] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is [ka] Selected from.

[0148] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (a) [ka] Selected from; R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl, Y 1 CR 3 Y 2 If it is N, then R A is -OR 11 Further selection from; R 11 Independently, hydrogen and C exist in each of their respective forms. 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl groups; p is either 0 or 1, where Y 1 CR 3 Y 2 N is Y 3 CR 4Y 4 If is N, then p is 0; X is N, CH, and CR 5 Selected from; R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Selected from haloalkyl groups.

[0149] In some embodiments, ring B is (a) [ka] Selected from; R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from; Y 1 CR 3 Y 2 If it is N, then R A These are -OH, -OCH3, and [ka] Further selection from;X 1 These are N, CH, and CR 5 R5 is selected from -F and -CH3; p is 0 or 1, except Y 1 CR 3 Y 2 N is Y 3 CR 4 Y 4 If p is N, then p is 0.

[0150] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is [ka] Selected from.

[0151] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] That is the case.

[0152] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] That is the case.

[0153] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (b) [ka] Selected from, X 2 S and NR 7 Selected from; q is either 0 or 1; R 6 is halogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 7 is hydrogen, C 1-4 Alkyl and C 1-4Selected from haloalkyl groups.

[0154] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from each [ka] The elements are selected from single or double bonds such that ring B forms an aromatic bicyclic ring system; R 8 is halogen, C 2-4 Alkyl and C 1-4 Selected from haloalkyls, R 9 is hydrogen, halogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyl; r is either 0 or 1.

[0155] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from each [ka] Ring B is selected from single or double bonds such that it forms an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; R 9 It is selected from hydrogen and -CH3; r is 0.

[0156] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is [ka] Selected from. In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] That is the case.

[0157] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), at least one of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) applies: (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (vi) Ring B is (c); (vii)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 is N; and (viii)Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 Therefore, ring B is either (a) or (c).

[0158] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from. In some embodiments, Y 1 S is Y 2 C is C, and ring B is (a), X 1 In some embodiments, Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl. In some embodiments, ring B is (a) and p is 1, 2, or 3. In some embodiments, R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl. In some embodiments, ring B is (c). In some embodiments, Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 In some embodiments, Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 Therefore, ring B is either (a) or (c).

[0159] In some embodiments, one or more of (i), (ii), (iv), and (v) (e.g., 1 to 3 (e.g., 1 to 2 (e.g., 1))) apply: (vii) Ring B is (a) and RA is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (viii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (ix)Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (x) Ring B is (a), where p is 1, 2, or 3; (xi)R 1 C 1-4 It is alkyl; and (xii) Ring B is (c).

[0160] In some embodiments, ring B is [ka] (In the formula, X 3 is selected from S and N, X 4 O and CR 9 Selected from each [ka] (where ring B represents a single or double bond such that it forms an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Selected from haloalkyl and -CN; R 9 is hydrogen and C 1-4 Selected from alkyl groups; p is selected from 0 and 1; r is selected from 0 and 1.

[0161] In some embodiments, ring B is [ka] (In the formula, X 1 These are N, CH, and CR 5 (Selected from)

[0162] In some embodiments, when a compound of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2) is subject to at least one of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii): (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (vi) Ring B is (c); (vii)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y4 is N; and (viii)Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 And ring B is (a) or (c); Ring A contains one or more halogens, C 1-6 Alkyl or cyclopropyl substituted with -CN;C 4-12 A carbon ring; and selected from 3- to 12-membered heterocycles; any of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups; However, ring B is (a), X1 is CH, and R A is methyl, Y 1CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl; if ring B is selected from (b), then ring A is not chroman.

[0163] In some embodiments, when a compound of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2) is subject to at least one of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii): (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (vi) Ring B is (c); (vii)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 is N; and (viii)Y 1N is Y 2 N is Y 3 CR 4 Y 4 CR 3 And ring B is (a) or (c); Ring A contains one or more halogens, C 1-6 Cyclopropyl substituted with alkyl or -CN, C 4-12 Selected from carbon rings and 3- to 12-membered heterocycles, any of which are halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups; However, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl; if ring B is selected from (b), then ring A is not chroman.

[0164] In some embodiments, when a compound of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2) is subject to at least one of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii): (i) Ring B is (a) and R A is halogen, C 1-4Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 selected from; (ii) Y 1 is S, Y 2 is C, ring B is (a), X 1 is N; (iii) Y 1 is S, Y 2 is C, ring B is (a), R A is C 1-4 alkyl; (iv) Ring B is (a), p is 1, 2, or 3; (v) R 1 is C 1-4 alkyl or C 1-4 haloalkyl; (vi) Ring B is (c); (vii) Y 1 is CR 3 is Y 2 is N, Y 3 is CR 3 is Y 4 is N; and (viii) Y 1 is N, Y 2 is N, Y 3 is CR 4 is Y 4 is CR 3 is ring B (a) or (c); Ring A is selected from cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, sulfolanyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is halogen, C 1-6Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl and phenyl.

[0165] In some embodiments, when a compound of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2) is subject to at least one of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii): (ix) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (x)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (xi)Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (xii) Ring B is (a), where p is 1, 2, or 3; (xiii)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (xiv) Ring B is (c); (xv)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 is N; and (xvi)Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 And ring B is (a) or (c); Ring A is selected from cyclopropyl, cyclobutyl, cyclohexyl, phenyl, oxepanyl, sulforanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is -F, -OH, -OCH3, -CH3, -CF3, =O, -CN, [ka] It is optionally substituted with one or more substituents selected independently of it.

[0166] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), m is selected from 0 and 1. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, p is selected from 0 and 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, q is selected from 0 and 1. In some embodiments, q is 0. In some embodiments, q is 1. In some embodiments, r is selected from 0 and 1. In some embodiments, r is 0. In some embodiments, r is 1.

[0167] In some embodiments, the compound is of formula (IIA-3): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from)

[0168] In some embodiments, the compound is of formula (IIB-3): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from)

[0169] In some embodiments, the compound is of formula (IIB-3): [ka] or a pharmaceutically acceptable salt thereof (wherein ring A is C 3-6They are carbon rings and 3- to 6-membered heterocycles, each of which is substituted with one or more halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 (It is optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle.)

[0170] In some embodiments, the compound is of formula (IIB-4): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from)

[0171] In some embodiments, the compound is of formula (IIC-3): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from)

[0172] In some embodiments, the compound is of formula (ID-3): [ka] or a pharmaceutically acceptable salt thereof.

[0173] In some embodiments, the compound is of formula (IIB-5): [ka] or a pharmaceutically acceptable salt thereof.

[0174] In some embodiments, the compound is of formula (IIB-6). [ka] or a pharmaceutically acceptable salt thereof.

[0175] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is One or more C 1-6 Cyclopropyl substituted with alkyl or -CN, C substituted with one or more halogens 3-6 Carbon ring, 3- to 6-membered heterocycle substituted with one or more halogens, C 5-6 Spirocyclic carbocyclic rings, and 5-6 membered spirocyclic heterocyclic rings (either of these is C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle); C 7-12 Carbon rings and 7-12 membered heterocycles (each of these being halogens, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle, provided that if ring B is selected from (b), then ring A is not chroman. Selected from; However, if one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then ring A is C 4-6 Further selections are made from carbon rings and 3- to 6-membered heterocycles, each of which is C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles: (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (vi) Ring B is (c); and (vii)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 is N; (viii)Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 And ring B is (a) or (c); However, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups.

[0176] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is C 4-12 Carbon rings and 3- to 12-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle, provided that if ring B is selected from (b), then ring A is not chroman. Selected from; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups.

[0177] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is C 4-12 Carbon rings and 3- to 12-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 A 3-6 membered heterocycle is optionally substituted with alkyl groups, and is optionally substituted with 1-4 substituents independently selected from these groups, provided that if ring B is selected from (b), then ring A is not chroman. Selected from; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups.

[0178] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is C 4-12 Selected from carbon rings and 3- to 12-membered heterocycles, each of which is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl, however, if ring B is selected from (b), then ring A is not chroman. In some embodiments, ring A is C 4-12 Selected from carbon rings and 3- to 12-membered heterocycles, each of which is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and 1 to 4 C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 It is selected from alkyl groups, provided that ring B is selected from (b), in which case ring A is not chroman.

[0179] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is C 4-6 Carbon rings and 3- to 6-membered heterocycles (each of which is substituted with one or more -F atoms, halogens, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle); 7-12 membered heterocycles (each of these being a halogen, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, -CN are optionally substituted with one or more substituents independently selected from these, provided that if ring B is selected from (b), then ring A is not chroman. Selected from; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups.

[0180] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is C 4-6 Carbon rings and 3- to 6-membered heterocycles (each of which is substituted with one or more -F atoms, halogens, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 It is optionally substituted with 1 to 4 substituents independently selected from an alkyl-substituted 3 to 6-membered heterocycle; 7-12 membered heterocycles (each of these being a halogen, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O is optionally substituted with one or more substituents independently selected from O, provided that if ring B is selected from (b), then ring A is not chroman. Selected from; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups.

[0181] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is saturated C 3-6 A carbon ring or a saturated 3- to 6-membered heterocycle, each of which is substituted with one or more halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 It is optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle. In some embodiments, ring A is saturated C 3-6 A saturated 3- to 6-membered heterocycle containing a carbon ring or one O ring member, each of which is substituted with one or more halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 It is optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle.

[0182] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is substituted with one or more halogens, and C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 A C atom optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle. 3-6 It is a carbon ring. In some embodiments, ring A is substituted with one -F and C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 A C atom optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle. 3-5 It is a carbon ring. In some embodiments, ring A is substituted with one -F and C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4 A 5-6 membered heterocycle optionally substituted with one or more substituents independently selected from an alkyl-substituted 3-6 membered heterocycle. In some embodiments, ring A is C 3-6 Selected from carbon rings and 3- to 6-membered heterocycles, each of which is substituted with one or more halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4It is optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle.

[0183] In some embodiments, for compounds of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), the heterocycle of ring A contains 1 to 4 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring A contains 1 to 3 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring A contains 1 to 2 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring A contains 2 to 3 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring A contains 1 heteroatom independently selected from O, N, and S. In some embodiments, the heterocycle of ring A contains 2 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring A contains 3 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring A contains 4 heteroatoms independently selected from O, N, and S.

[0184] In some embodiments, for compounds of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), the heterocycle of ring A contains 1 to 4 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring A contains 1 to 3 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring A contains 1 to 2 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring A contains 2 to 3 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring A contains 1 heteroatom independently selected from O and N. In some embodiments, the heterocycle of ring A contains 2 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring A contains 3 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring A contains 4 heteroatoms independently selected from O and N.

[0185] In some embodiments, for compounds of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), the heterocycle of ring A contains four N heteroatoms. In some embodiments, the heterocycle of ring A contains three N heteroatoms. In some embodiments, the heterocycle of ring A contains three N heteroatoms and one O heteroatom. In some embodiments, the heterocycle of ring A contains two N heteroatoms and one O heteroatom. In some embodiments, the heterocycle of ring A contains two N heteroatoms and one S heteroatom. In some embodiments, the heterocycle of ring A contains one O heteroatom and one N heteroatom. In some embodiments, the heterocycle of ring A contains one O heteroatom and one S heteroatom. In some embodiments, the heterocycle of ring A contains one S heteroatom and one N heteroatom. In some embodiments, the heterocycle of ring A contains two N heteroatoms. In some embodiments, the heterocycle of ring A contains one heteroatom that is O. In some embodiments, the heterocycle of ring A contains one heteroatom that is N. In some embodiments, the heterocycle of ring A contains one heteroatom that is S.

[0186] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A as described herein is substituted with 1 to 4 substituents as described herein. In some embodiments, ring A as described herein is unsubstituted.

[0187] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Cyclopropyl groups substituted with one or more -CH3 or -CN atoms, optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; Cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinylpyrrolidinyl, and piperidinyl (each of these is substituted with one or more -F, halogens, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles); and Spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl (any of these are halogens, C 1-6 Alkyl, C 1-6Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, -CN, and one or more C 1-4 (Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle.) Selected from; However, if one or more of (i), (ii), (iv), (v), (vi), (vii), and (viii) apply, then ring A is further selected from cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranil, tetrahydropyranil, oxepanil, sulforanil, azetidinil, pyrrolidinil, piperidinil, spiro[2.2]pentanil, spiro[3.2]hexanil, spiro[4.2]heptanil, 6-oxaspiro[2.5]octanil, 2-oxabicyclo[2.2.1]heptanil, 8-oxabicyclo[3.2.1]octanil, 1-oxaspiro[5.5]undecanil, adamantanil, 2-azaspiro[3.3]heptanil, and 1,9-dioxaspiro[5.5]undecanil, each of which is a halogen, C 1-6 Alkyl, -C(O)OR 12 , and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (vi) Ring B is (c); and (vii)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 is N; (viii)Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 And ring B is (a) or (c); However, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups.

[0188] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is Cyclopropyl substituted with one or more -CH3 or -CN groups; Cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinylpyrrolidinyl, and piperidinyl (each of these is substituted with one or more -F, -OH, -OCH3, -CH3, [ka] Optionally substituted with one or more substituents independently selected from; and Spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl (any of these may be optionally substituted with one or more substituents independently selected from -F, -OH, and -CH3). Selected from, However, if one or more of (i), (ii), (iv), (v), (vi), (vii), and (viii) apply, then ring A is cyclobutyl, cyclohexyl, phenyl, oxepanyl, sulforanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2 Further selections are made from ]heptanyl, 6-oxaspiro[2.5]octanyl, 2-oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is -F, -OH, -OCH3, -CH3, -CF3, =O, [ka] Optionally substituted with one or more substituents independently selected from; (i) Ring B is (a) and R A is halogen, C 1-4Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (vi) Ring B is (c); and (vii)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 is N; (viii)Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 And ring B is (a) or (c); However, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is selected from tetrahydrofuranyl substituted only with methyl groups.

[0189] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is selected from phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl; pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups. In some embodiments, ring A is selected from phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl;pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Optionally substituted with 1 to 4 substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups.

[0190] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is selected from phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is a halogen, C 1-6 Alkyl, -C(O)OR 12 , and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups. In some embodiments, ring A is selected from phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is a halogen, C 1-6 Alkyl, -C(O)OR 12 , and one or more C 1-4 Optionally substituted with 1 to 4 substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups.

[0191] In some embodiments, for compounds of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), the halogen substituent on ring A is bonded to a member of ring A that is -L-bonded. In some embodiments, the -F substituent on ring A is bonded to a member of ring A that is -L-bonded.

[0192] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is Cyclopropyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinylpyrrolidinyl, and piperidinyl (each of these is substituted with one or more -F, halogen, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle); Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 121,9-dioxaspiro[5.5]undecanyl, optionally substituted with one or more substituents independently selected from ,=O, and -CN. Selected from; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups.

[0193] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is Cyclopropyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinylpyrrolidinyl, and piperidinyl (each of these is substituted with 1 to 4 -F atoms, halogens, and C atoms). 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles); and Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 1,9-dioxaspiro[5.5]undecanyl, optionally substituted with one or more substituents independently selected from ,=O, and -CN. Selected from; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups.

[0194] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is selected from cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl; pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is -F, -OH, -CH3, [ka] It is optionally substituted with one or more substituents independently selected from the ring. In some embodiments, ring A is selected from cyclopropyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl;pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is -F, -CH3, [ka] It is optionally substituted with one or more substituents independently selected from the ring. In some embodiments, ring A is selected from cyclopropyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl;pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is -F, -CH3, [ka] It is optionally substituted with 1 to 4 substituents independently selected from the ring. In some embodiments, ring A is -F, -CH3, [ka] It is a cyclopropyl ring optionally substituted with 1 to 4 substituents independently selected from -F and -CH3. In some embodiments, ring A is a cyclopropyl ring optionally substituted with 1 to 4 substituents independently selected from -F and -CH3.

[0195] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is -F, -CH3, [ka] Phenyl is optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring A is -F, -CH3, [ka] It is a tetrahydrofuranyl optionally substituted with 1 to 4 substituents independently selected from -F and -CH3. In some embodiments, ring A is a tetrahydrofuranyl optionally substituted with 1 to 4 substituents independently selected from -F and -CH3.

[0196] In some embodiments, ring A is -F, -CH3, [ka] It is a tetrahydropyranyl optionally substituted with 1 to 4 substituents independently selected from -F and -CH3. In some embodiments, ring A is a tetrahydropyranyl optionally substituted with 1 to 4 substituents independently selected from -F and -CH3.

[0197] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is -F, -CH3, [ka] Azetidinyl is optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring A is -F, -CH3, [ka] A pyrrolidinyl optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring A is -F, -CH3, [ka] A piperidinyl optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring A is -F, -CH3, [ka] It is 1,9-dioxaspiro[5.5]undecanyl, optionally substituted with 1 to 4 substituents independently selected from the above.

[0198] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is [ka] [ka] Selected from.

[0199] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is One or more C 1-6 Cyclopropyl substituted with alkyl or -CN, C substituted with one or more halogens 3-6 Carbon ring, 3- to 6-membered heterocycle substituted with one or more halogens, C 5-6 Spirocyclic carbocyclic rings, and 5-6 membered spirocyclic heterocyclic rings (either of these is C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and one or more C 1-4Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle); C 7-12 Carbon rings and 7-12 membered heterocycles (each of these being halogens, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle, provided that if ring B is selected from (b), then ring A is not chroman. Selected from; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups.

[0200] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is One or more halogens, C 1-6 Cyclopropyl substituted with alkyl or -CN; Cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranil, tetrahydropyranil, azetidinylpyrrolidinil, and piperidinil (each of which is substituted with one or more halogens); and Spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl Selected from; Any of these is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; R 12 Independently, hydrogen and C exist in each of their respective forms. 1-6 Selected from alkyl groups.

[0201] In some embodiments, if ring B is selected from (b) for any of the compounds of the preceding formula, then ring A is not chroman.

[0202] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is Cyclopropyl substituted with one or more -F, -CH3, or -CN groups; Cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranil, tetrahydropyranil, azetidinylpyrrolidinil, and piperidinil (each of these substituted with one or more -F); and Spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl Selected from; Any of these is -F, -OH, -OCH3, -CH3, -CF3, =O, -CN, [ka] It is optionally substituted with one or more substituents selected independently of it.

[0203] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is [ka] Selected from.

[0204] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is [ka] Selected from.

[0205] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is [ka] Selected from.

[0206] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is [ka] Selected from.

[0207] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is [ka] Selected from.

[0208] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] That is the case.

[0209] In some embodiments, for compounds of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is tetrahydropyranyl optionally substituted with 1 to 4 halogens. In some embodiments, ring A is tetrahydropyranyl optionally substituted with 1 to 4 halogens. In some embodiments, ring A is tetrahydropyranyl optionally substituted with 1 to 4 fluorines. In some embodiments, ring A is tetrahydropyranyl optionally substituted with 1 to 4 fluorines. In some embodiments, ring A is a tetrahydropyranyl optionally substituted with one halogen. In some embodiments, ring A is a tetrahydropyranyl optionally substituted with one fluorine. In some embodiments, ring A is a tetrahydropyranyl substituted with one fluorine. In some embodiments, ring A is an unsubstituted tetrahydropyranyl. In some embodiments, ring A has 1 to 4 carbon atoms. 1-6 It is a tetrahydropyranyl optionally substituted with alkyl. In some embodiments, ring A has 1 to 4 C 1-6 It is an alkyl-substituted tetrahydropyranyl. In some embodiments, ring A is a tetrahydropyranyl optionally substituted with 1 to 4 methyl groups. In some embodiments, ring A is a tetrahydropyranyl substituted with 1 to 4 methyl groups. In some embodiments, ring A is a 1 C 1-6 It is a tetrahydropyranyl optionally substituted with an alkyl group. In some embodiments, ring A is a single C 1-6It is an alkyl-substituted tetrahydropyranyl. In some embodiments, ring A is a tetrahydropyranyl optionally substituted with one methyl group. In some embodiments, ring A is a tetrahydropyranyl substituted with one methyl group. In some embodiments, ring A has four C 1-6 It is an optionally alkyl-substituted tetrahydropyranyl. In some embodiments, ring A has four C 1-6 It is an alkyl-substituted tetrahydropyranyl. In some embodiments, ring A is a tetrahydropyranyl optionally substituted with four methyl groups. In some embodiments, ring A is a tetrahydropyranyl substituted with four methyl groups.

[0210] In some embodiments, for compounds of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is an unsubstituted tetrahydrofuranyl. In some embodiments, ring A has 1 to 4 C 1-6 It is a tetrahydrofuranyl optionally substituted with alkyl. In some embodiments, ring A has 1 to 4 C 1-6 It is an alkyl-substituted tetrahydrofuranyl. In some embodiments, ring A is a tetrahydrofuranyl optionally substituted with 1 to 4 methyl groups. In some embodiments, ring A is a tetrahydrofuranyl substituted with 1 to 4 methyl groups. In some embodiments, ring A is a 1C 1-6 It is a tetrahydrofuranyl optionally substituted with an alkyl group. In some embodiments, ring A is a single C 1-6 It is an alkyl-substituted tetrahydrofuranyl. In some embodiments, ring A is a tetrahydrofuranyl optionally substituted with one methyl group. In some embodiments, ring A is a tetrahydrofuranyl substituted with one methyl group. In some embodiments, ring A has four C1-6 It is a tetrahydrofuranyl optionally substituted with alkyl. In some embodiments, ring A has four C 1-6 It is an alkyl-substituted tetrahydrofuranyl. In some embodiments, ring A is a tetrahydrofuranyl optionally substituted with four methyl groups. In some embodiments, ring A is a tetrahydrofuranyl substituted with four methyl groups.

[0211] In some embodiments, the compound is of formula (IIIA): [ka] or a pharmaceutically acceptable salt thereof (wherein R 5 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 Selected from; R 16 is halogen, -OR 12 , and C optionally substituted with 1 to 4 halogens 1-6 Selected from alkyl groups; Q is O, NH, or S.

[0212] In some embodiments, the compound is of formula (IIIB). [ka] or a pharmaceutically acceptable salt thereof (wherein R 16 is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 Selected from; Q is O, NH, or S). In some embodiments, Q is O.

[0213] In some embodiments, the compound is of formula (IIIA-1): [ka] or a pharmaceutically acceptable salt thereof (wherein R 5 is hydrogen, C 1-6Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 Selected from; R 16 is halogen, -OR 12 , and C optionally substituted with 1 to 4 halogens 1-6 Selected from alkyl groups; Q is O, NH, or S.

[0214] In some embodiments, the compound is of formula (IIIB-1): [ka] or a pharmaceutically acceptable salt thereof (wherein R 16 is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 Selected from; Q is O, NH, or S. In some embodiments, Q is O. In some embodiments, p is 0.

[0215] In some embodiments, the compound is of formula (IIIC-1): [ka] or a pharmaceutically acceptable salt thereof (wherein R 16 is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 Selected from; Q is O, NH, or S). In some embodiments, Q is O.

[0216] In some embodiments, the compound is of formula (IIIA-2): [ka] or a pharmaceutically acceptable salt thereof (wherein R 5 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 Selected from; R16 is halogen, -OR 12 , and C optionally substituted with 1 to 4 halogens 1-6 Selected from alkyl groups; Q is O, NH, or S.

[0217] In some embodiments, the compound is of formula (IIIA-3): [ka] or a pharmaceutically acceptable salt thereof (wherein R 5 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 Selected from; R 16 is halogen, -OR 12 , and C optionally substituted with 1 to 4 halogens 1-6 Selected from alkyl groups; Q is O, NH, or S.

[0218] In some embodiments, the compound is of formula (IIIA-4): [ka] or a pharmaceutically acceptable salt thereof (wherein R 5 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 Selected from; R 16 is halogen, -OR 12 , and C optionally substituted with 1 to 4 halogens 1-6 Selected from alkyl groups; Q is O, NH, or S.

[0219] In some embodiments, the compound is of formula (IIIA-5): [ka] or a pharmaceutically acceptable salt thereof (wherein R 5 is hydrogen, C 1-6 Alkyl, C 1-6Haloalkyl and -C(O)OR 12 Selected from; R 16 is halogen, -OR 12 , and C optionally substituted with 1 to 4 halogens 1-6 Selected from alkyl groups; Q is O, NH, or S.

[0220] In some embodiments, for compounds of formula (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), or (IIIC-1), R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -OR 11 , -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl groups; R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl groups; R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 Selected from , and -CN, R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 Selected from , and -CN, R 11 is hydrogen, and C 1-4 Selected from alkyl groups. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 1-4 Selected from hydroxyalkyl groups. In some embodiments, R A is halogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R A is halogen and C 1-4 Selected from alkyl groups. In some embodiments, R A C 1-4 Selected from alkyl groups.

[0221] In some embodiments, for compounds of formula (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), or (IIIC-1), R A -F, -Cl, -CN, -NH2, -OH, -OCH3, [ka] -CH3, -CF3, -CHF2, [ka] Selected from. In some embodiments, R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from. In some embodiments, R A R is selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, and -CHF2. In some embodiments, R A R is selected from -F, -Cl, -CH3, -CF3, and -CHF2. In some embodiments, R A R is selected from -F and -Cl. In some embodiments, R A R is selected from -CH3, -CF3, and -CHF2. In some embodiments, R A It is selected from -CH3.

[0222] In some embodiments, for compounds of formula (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), or (IIIC-1), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1.

[0223] In some embodiments, for compounds of formula (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), or (IIIC-1), R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-C(O)N(R13 )2, -N(R 13 )C(O)R 13 , -N(R 13 )S(O)2(R 13 ), -S(O)2R 13 -S(O)2N(R 13 )2, -NO2, and -CN are selected. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -SR 13 , -N(R 13 )2, -C(O)OR 13 ,-OC(O)R 13 ,-C(O)N(R 13 )2, -N(R 13 )C(O)R 13 Selected from , and -CN. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -SR 13 , -N(R 13 )2, and -CN are selected. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Selected from haloalkyl and -CN. In some embodiments, R 5 is a halogen. In some embodiments, R 5 C 1-4 It is alkyl. In some embodiments, R 5 C 1-4 In some embodiments, R 5 is -OR 13 In some embodiments, R 5 -SR 13 In some embodiments, R 5 is -N(R 13 )2. In some embodiments, R 5 is -C(O)R 13 In some embodiments, R 5 is -C(O)OR13 In some embodiments, R 5 is -OC(O)R 13 In some embodiments, R 5 is -C(O)N(R 13 )2. In some embodiments, R 5 is -N(R 13 )C(O)R 13 In some embodiments, R 5 is -N(R 13 )S(O)2(R 13 ) is. In some embodiments, R 5 is -S(O)2R 13 In some embodiments, R 5 is -S(O)2N(R 13 )2. In some embodiments, R 5 is -NO2. In some embodiments, R 5 It is -CN.

[0224] In some embodiments, the compound is of formula (IIIB-2): [ka] or a pharmaceutically acceptable salt thereof (wherein R 16 is halogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; Q is O, NH, or S). In some embodiments, Q is O. In some embodiments, R 16 is selected from -F and -CH3; Q is O; X 1 It is either CH or N.

[0225] In some embodiments, the compound is of formula (IIIB-3): [ka] or a pharmaceutically acceptable salt thereof (wherein R 16 is halogen, C 1-4 Alkyl and C 1-4Selected from haloalkyl groups; Q is O, NH, or S). In some embodiments, Q is O. In some embodiments, R 16 is selected from -F and -CH3; Q is O; X 1 It is either CH or N.

[0226] In some embodiments, for compounds of formula (IIIA), (IIIA-1), (IIIB), (IIIB-1), (IIIB-2), (IIIB-3), or (IIIC-1), X 1 These are N, CH, and CR 5 Selected from. In some embodiments, X 1 This is selected from N and CH. In some embodiments, X 1 CH and CR 5 Selected from. In some embodiments, X 1 In some embodiments, X 1 is CH. In some embodiments, X 1 CR 5 That is the case.

[0227] In some embodiments, for compounds of formula (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), (IIIB-2), (IIIB-3), or (IIIC-1), Q is O, NH, or S. In some embodiments, Q is O.

[0228] In some embodiments, for compounds of formula (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), (IIIB-2), (IIIB-3), or (IIIC-1), each R 16 is halogen, C 1-4 Alkyl and C 1-4 Selected independently from haloalkyls. In some embodiments, each R 16 is halogen and C 1-4Selected independently of alkyl. In some embodiments, each R 16 is halogen and C 1-4 Selected independently of alkyl. In some embodiments, each R 16 -F and C 1-4 Selected independently of alkyl. In some embodiments, each R 16 is selected independently from -F and -CH3. In some embodiments, each R 16 C 1-4 Selected independently of alkyl. In some embodiments, each R 16 is -CH3. In some embodiments, each R 16 The halogen is selected independently of the halogen. In some embodiments, each R 16 It is -F.

[0229] In some embodiments, for compounds of formula (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), (IIIB-2), (IIIB-3), or (IIIC-1), the compound has 0, 1, 2, 3, or 4 R 16 It has a group. In some embodiments, the compound has 0, 1, 2, or 3 R groups. 16 It has a group. In some embodiments, the compound has 0, 1, or 2 R groups. 16 It has a group. In some embodiments, the compound has 0 or 1 R 16 It has a group. In some embodiments, the compound has 1, 2, 3, or 4 R groups. 16 It has a group. In some embodiments, the compound has 1, 2, or 3 R groups. 16 It has a group. In some embodiments, the compound has one or two R groups. 16 It has a group. In some embodiments, the compound has 0 R 16 It has a group. In some embodiments, the compound has one R 16 It has a group. In some embodiments, the compound has two R groups. 16 It has a group. In some embodiments, the compound has three R groups. 16It has a group. In some embodiments, the compound has four R groups. 16 It has a base.

[0230] In some embodiments, for compounds of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2), (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), ring A is a cyclopropyl optionally substituted with 1 to 4 halogens. In some embodiments, ring A is a cyclopropyl optionally substituted with 1 to 4 halogens. In some embodiments, ring A is a cyclopropyl optionally substituted with 1 to 4 fluorines. In some embodiments, ring A is a cyclopropyl optionally substituted with 1 halogen. In some embodiments, ring A is a cyclopropyl substituted with one halogen. In some embodiments, ring A is a cyclopropyl optionally substituted with one fluorine. In some embodiments, ring A is a cyclopropyl substituted with one fluorine. In some embodiments, ring A is not chroman.

[0231] In some embodiments, the compound is of formula (IVA): [ka] or a pharmaceutically acceptable salt thereof (wherein R 15 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0232] In some embodiments, the compound is of formula (IVA-1): [ka] or a pharmaceutically acceptable salt thereof (wherein R 15 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0233] In some embodiments, the compound is of formula (IVB-1): [ka] or a pharmaceutically acceptable salt thereof (wherein R 15 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0234] In some embodiments, the compound is of formula (IVA-2): [ka] or a pharmaceutically acceptable salt thereof (wherein R 15 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0235] In some embodiments, the compound is of formula (IVA-3): [ka] or a pharmaceutically acceptable salt thereof (wherein R 15 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0236] In some embodiments, for compounds of formula (IVA), (IVA-1), (IVA-2), (IVA-3), or (IVB-1), R A is halogen, C1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -OR 11 , -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl groups; R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl groups; R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 Selected from , and -CN, R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR11 , -N(R 11 )C(O)R 11 Selected from , and -CN, R 11 is hydrogen, and C 1-4 Selected from alkyl groups. In some embodiments, R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 1-4 Selected from hydroxyalkyl groups. In some embodiments, R A is halogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R A is halogen and C 1-4 Selected from alkyl groups. In some embodiments, R A C 1-4 Selected from alkyl groups.

[0237] In some embodiments, for compounds of formula (IVA), (IVA-1), (IVA-2), (IVA-3), or (IVB-1), R A -F, -Cl, -CN, -NH2, -OH, -OCH3, [ka] -CH3, -CF3, -CHF2, [ka] Selected from. In some embodiments, R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from. In some embodiments, R A R is selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, and -CHF2. In some embodiments, R A R is selected from -F, -Cl, -CH3, -CF3, and -CHF2. In some embodiments, RA R is selected from -F and -Cl. In some embodiments, R A R is selected from -CH3, -CF3, and -CHF2. In some embodiments, R A It is selected from -CH3.

[0238] In some embodiments, for compounds of formula (IVA), (IVA-1), (IVA-2), (IVA-3), or (IVB-1), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1.

[0239] In some embodiments, for compounds of formula (IVA), (IVA-1), (IVA-2), (IVA-3), or (IVB-1), R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -N(R 13 )S(O)2(R 13 ), -S(O)2R 13 -S(O)2N(R 13 )2, -NO2, and -CN are selected. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -SR 13 , -N(R 13 )2, -C(O)OR 13 ,-OC(O)R 13 ,-C(O)N(R 13 )2, -N(R 13 )C(O)R 13 Selected from , and -CN. In some embodiments, R 5Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -SR 13 , -N(R 13 )2, and -CN are selected. In some embodiments, R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Selected from haloalkyl and -CN. In some embodiments, R 5 is a halogen. In some embodiments, R 5 C 1-4 It is alkyl. In some embodiments, R 5 C 1-4 In some embodiments, R 5 is -OR 13 In some embodiments, R 5 -SR 13 In some embodiments, R 5 is -N(R 13 )2. In some embodiments, R 5 is -C(O)R 13 In some embodiments, R 5 is -C(O)OR 13 In some embodiments, R 5 is -OC(O)R 13 In some embodiments, R 5 is -C(O)N(R 13 )2. In some embodiments, R 5 is -N(R 13 )C(O)R 13 In some embodiments, R 5 is -N(R 13 )S(O)2(R 13 ) is. In some embodiments, R 5 is -S(O)2R 13 In some embodiments, R 5 is -S(O)2N(R 13 )2. In some embodiments, R 5 is -NO2. In some embodiments, R5 It is -CN.

[0240] In some embodiments, R A C 1-4 It is alkyl. In some embodiments, R 16 is selected from -F and -CH3; Q is O; X 1 is CH or N. In some embodiments, p is 0.

[0241] In some embodiments, the compound is of formula (IVA-4): [ka] or a pharmaceutically acceptable salt thereof (wherein R 15 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0242] In some embodiments, the compound is of formula (IVB-2): [ka] or a pharmaceutically acceptable salt thereof (wherein R 15 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0243] In some embodiments, the compound is of formula (IVB-3): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 is CH or N, and R 15 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0244] In some embodiments, the compound is of formula (IVB-4): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 is CH or N, and R 15 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0245] In some embodiments, for compounds of formula (IVA), (IVA-1), (IVA-2), (IVA-3), (IVA-4), (IVB-1), (IVB-2), (IVB-3), or (IVB-4), X 1 These are N, CH, and CR 5 Selected from. In some embodiments, X 1 This is selected from N and CH. In some embodiments, X 1 CH and CR 5 Selected from. In some embodiments, X 1 In some embodiments, X 1 is CH. In some embodiments, X 1 CR 5 That is the case.

[0246] In some embodiments, for compounds of formula (IVA), (IVA-1), (IVA-2), (IVA-3), (IVA-4), (IVB-1), (IVB-2), (IVB-3), or (IVB-4), X 1 CR 5 And R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -SR 13 , -N(R 13 )2, and -CN are selected. In some embodiments, X 1 CR 5 And R5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Selected from haloalkyl and -CN. In some embodiments, X 1 CR 5 And R 5 is a halogen. In some embodiments, X 1 CR 5 And R 5 C 1-4 It is alkyl. In some embodiments, X 1 CR 5 And R 5 C 1-4 It is a haloalkyl group.

[0247] In some embodiments, the compound is of formula (IVA-5): [ka] or a pharmaceutically acceptable salt thereof (wherein R 15 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)OR 12 (Selected from)

[0248] In some embodiments, for compounds of formula (IVA), (IVA-1), (IVA-2), (IVA-3), (IVA-4), (IVA-5), (IVB-1), (IVB-2), (IVB-3), or (IVB-4), each R 15 is halogen, C 1-4 Alkyl and C 1-4 Selected independently from haloalkyls. In some embodiments, each R 15 is halogen and C 1-4 Selected independently of alkyl. In some embodiments, each R 15 is halogen and C 1-4 Selected independently of alkyl. In some embodiments, each R 15 -F and C 1-4 Selected independently of alkyl. In some embodiments, each R15 is selected independently from -F and -CH3. In some embodiments, each R 15 C 1-4 Selected independently of alkyl. In some embodiments, each R 15 is -CH3. In some embodiments, each R 15 The halogen is selected independently of the halogen. In some embodiments, each R 15 is -F. In some embodiments, R 15 is hydrogen. In some embodiments, R 15 C 1-6 It is alkyl. In some embodiments, R 15 C 1-6 In some embodiments, R 15 is -C(O)OR 12 That is the case.

[0249] In some embodiments, for compounds of formula (IVA), (IVA-1), (IVA-2), (IVA-3), (IVA-4), (IVA-5), (IVB-1), (IVB-2), (IVB-3), or (IVB-4), the compound has 0, 1, 2, 3, or 4 R 15 It has a group. In some embodiments, the compound has 0, 1, 2, or 3 R groups. 15 It has a group. In some embodiments, the compound has 0, 1, or 2 R groups. 15 It has a group. In some embodiments, the compound has 0 or 1 R 15 It has a group. In some embodiments, the compound has 1, 2, 3, or 4 R groups. 15 It has a group. In some embodiments, the compound has 1, 2, or 3 R groups. 15 It has a group. In some embodiments, the compound has one or two R groups. 15 It has a group. In some embodiments, the compound has 0 R 15 It has a group. In some embodiments, the compound has one R 15 It has a group. In some embodiments, the compound has two R groups. 15 It has a group. In some embodiments, the compound has three R groups.15 It has a group. In some embodiments, the compound has four R groups. 15 It has a base.

[0250] In some embodiments, for any compound of the preceding formula, R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-6 Selected from alkyl groups. In some embodiments, R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-4 Selected from alkyl groups. In some embodiments, each R 10 is hydrogen and C 1-6 Selected independently of alkyl. In some embodiments, each R 10 R is independently hydrogen. In some embodiments, each R 10 Independently, C 1-6 It is alkyl. In some embodiments, each R 11 is hydrogen and C 1-6 Selected independently of alkyl. In some embodiments, each R 11 R is independently hydrogen. In some embodiments, each R 11 Independently, C 1-6 It is alkyl. In some embodiments, each R 12 is hydrogen and C 1-6 Selected independently of alkyl. In some embodiments, each R 12 R is independently hydrogen. In some embodiments, each R 12 Independently, C 1-6 It is alkyl. In some embodiments, each R 13 is hydrogen and C 1-6 Selected independently of alkyl. In some embodiments, each R 13 R is independently hydrogen. In some embodiments, each R 13Independently, C 1-6 It is alkyl. In some embodiments, each R 14 is hydrogen and C 1-6 Selected independently of alkyl. In some embodiments, each R 14 R is independently hydrogen. In some embodiments, each R 14 Independently, C 1-6 It is alkyl.

[0251] In some embodiments, the compound is of formula (IVA-6): [ka] or a pharmaceutically acceptable salt thereof.

[0252] In some embodiments, the compound is of formula (IVA-7): [ka] or a pharmaceutically acceptable salt thereof.

[0253] In some embodiments, the compound is of formula (IVA-8): [ka] or a pharmaceutically acceptable salt thereof.

[0254] In some embodiments, the compound is of formula (IIC-10): [ka] or a pharmaceutically acceptable salt thereof (in the formula, Ring B is selected from (a), (b), and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); (b) [ka] (X 2 S and NR 7 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] This represents single or double bonds such that ring B forms an aromatic bicyclic ring system. R 1 is hydrogen, C 1-4 -C(O)C optionally substituted with alkyl and one or more halogens. 3-6 Selected from cycloalkyl groups; R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R 10 ) Selected from NO2 and -CN; R 3 and R 4 These are, independently, hydrogen, halogen, and C in their respective existences. 1-4 Alkyl and C 1-4 Selected from haloalkyl; R A is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 -CN, -S(O)2C 1-4 Alkyl, C3-6 Selected from cycloalkyl and 3- to 6-membered heterocycloalkyl groups; Ring A is a cyclopropyl, C substituted with one or more halogens. 4-12 Selected from carbon rings and 3- to 12-membered heterocycles, each of which is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 Optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN; R 5 , R 6 , and R 8 Each of them independently contains halogens and C in their respective forms. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -N(R 13 )S(O)2(R 13 ), -S(O)2R 13-S(O)2N(R 13 ) Selected from -NO2 and -CN; R 7 and R 9 These are, independently, hydrogen and C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups; m is selected from 0, 1, and 2; p is selected from 0, 1, and 2; q is selected from 0, 1, and 2; (r is selected from 0, 1, and 2) That is the case.

[0255] In some embodiments, for the compound of formula (IIC-10), R A is halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 ,-CN,C 3-6 Selected from cycloalkyl and 3- to 6-membered heterocycloalkyl groups; Y 1 CR 3 Y 2 If it is N, then R A is -OR 11 Further selection from; R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl groups; R 5 Independently, in each presence, halogens and C1-4 Selected from alkyl groups; p is selected from 0 and 1.

[0256] In some embodiments, for the compound of formula (IIC-10), R A -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, [ka] Selected from; Y 1 CR 3 Y 2 If it is N, then R A These are -OH, -OCH3, and [ka] Further selections from; R 5 In each instance, it is selected from -F, -Cl, and -CH3; p is selected from 0 and 1.

[0257] In some embodiments, the compound of formula (II) is [ka] A compound of or a pharmaceutically acceptable salt thereof (wherein the formula, each [ka] Y 1 , Y 2 , and Y 3 A bicyclic ring system containing ((i)Y 1 CR 3 Y 2 (ii) Y 1 S is Y 2 This represents a single or double bond such that (C) is the case; Y 3 N and CR 4 Selected from; Ring B is selected from (a), (b), and (c): (a) [ka] (X 1 These are N, CH, and CR 5 Selected from); (b) [ka] (X 2 S and NR 7 Selected from); and (c) [ka] (X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] This represents single or double bonds such that ring B forms an aromatic bicyclic ring system. R 1 is hydrogen, C 1-4 Alkyl, C 1-4 -C(O)C optionally substituted with haloalkyl and one or more halogens. 3-6 Selected from cycloalkyl groups; R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -N(R 10 )2, and -CN are selected; R 3 and R 4 These are, independently, hydrogen, halogen, and C. 1-4 Alkyl and C 1-4 Selected from haloalkyl; R Ais halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, -N(R 11 )2, -SR 11 , -N(R 11 )C(O)R 11 -CN, -S(O)2C 1-4 Alkyl, C 3-6 Selected from cycloalkyl and 3-6 member heterocycloalkyl groups, however, Y 1 CR 3 Y 2 N is Y 4 CR 3 If Y 1 CR 3 Y 2 N is Y 4 If it is N, then R A is -OR 11 Further selections are made from these. Y 1 CR 3 Y 2 N is Y 3 is CH, ring B is (a), p is 0, X 1 If is N and ring A is 1-fluoro-1-tetrahydropyranyl, then R A It is further selected from hydrogen, Y 1 S is Y 2 C is X 1 If it is N, then R A It is further selected from hydrogen; Ring A contains one or more C 1-6 Cyclopropyl substituted with alkyl or -CN, C substituted with one or more halogens 3-6 Carbon ring, 3- to 6-membered heterocycle substituted with one or more halogens, C 5-6 Selected from spirocyclic carbon rings and 5-6 membered spirocyclic heterocycles, any of which are halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R12 )2, -C(O)R 12 , -C(O)OR 12 , =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles; C 7-12 Carbon rings and 7-12 membered heterocycles (each of these being halogens, C) 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from an alkyl-substituted 3- to 6-membered heterocycle, provided that if ring B is selected from (b), then ring A is not chroman); However, if one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then ring A is C 4-6 Further selections are made from carbon rings and 3- to 6-membered heterocycles, each of which is C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 , =O, -CN, and one or more C 1-4 A 3- to 6-membered heterocycle optionally substituted with alkyl; and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles: (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 Alkyl or C 1-4 It is a haloalkyl; (vi) Ring B is (c); and (vii)Y 1 CR 3 Y 2 N is Y 3 CR 3 Y 4 is N; (viii)Y 1 N is Y 2 N is Y 3 CR 4 Y 4 CR 3 And ring B is (a) or (c); However, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl; R 5 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl and -OR 13 Selected from, however, R A ga-OR 11 If that is the case, then R 5 is -OR 13 Not; R 6 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4Haloalkyl, -OR 14 , and -N(R 14 ) Selected from 2; R 7 is hydrogen and C 1-4 Selected from alkyl groups; R 8 Independently, in each presence, halogen, C 2-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , and -N(R 14 ) Selected from 2; R 9 is hydrogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 10 , R 11 , R 12 , R 13 , R 14 These are, independently, hydrogen and C in their respective existences. 1-4 Selected from alkyl groups; (m, p, q, and r are each independently selected from 0 and 1.) That is the case.

[0258] In some embodiments, for compounds of formula (I), (II), or their subformulas, Y 1 CR 3 Y 2 If it is N, then R A is -OR 11 Further selection from. In some embodiments, Y 1 CR 3 Y 2 is N; R A is -OR 11 Further selections are made from R A ga-OR 11 If that is the case, then R 5 is -OR 13 isn't it.

[0259] In some embodiments, for compounds of formula (I), (II), or their subformulas, Y 1 CR 3Y 2 N is Y 3 is CH, ring B is (a), p is 0, X 1 If is N and ring A is 1-fluoro-1-tetrahydropyranyl, then R A is further selected from hydrogen. In some embodiments, Y 1 CR 3 Y 2 N is Y 3 is CH, ring B is (a), p is 0, X 1 is N, and ring A is 1-fluoro-1-tetrahydropyranyl; R A It is further selected from hydrogen.

[0260] In some embodiments, for compounds of formula (I), (II), or their subformulas, Y 1 S is Y 2 C is X 1 If it is N, then R A is further selected from hydrogen. In some embodiments, Y 1 S is Y 2 C is X 1 is N; R A It is further selected from hydrogen.

[0261] In some embodiments, when one or more of (i), (ii), (ii), (iv), and (v) are applied to a compound of formula (I), (II), or a subformula thereof, then ring A is C 4-6 Further selections are made from carbon rings and 3- to 6-membered heterocycles, each of which is C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12)C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles: (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 It is alkyl; and (vi) Ring B is (c).

[0262] In some embodiments, one or more of (i), (ii), (ii), (iv), and (v) apply to compounds of formula (I), (II), or their subformulas; ring A is C 4-6 Further selections are made from carbon rings and 3- to 6-membered heterocycles, each of which is C 1-6 Alkyl, C 1-6 Haloalkyl, -OR12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, -CN, and one or more C 1-4 Optionally substituted with one or more substituents independently selected from alkyl-substituted 3- to 6-membered heterocycles: (i) Ring B is (a) and R A is halogen, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 11 , and -OR 11 Selected from; (ii)Y 1 S is Y 2 C is C, and ring B is (a), X 1 is N; (iii) Y 1 S is Y 2 C is and ring B is (a) and R A C 1-4 It is alkyl; (iv) Ring B is (a), where p is 1, 2, or 3; (v)R 1 C 1-4 It is alkyl; and (vi) Ring B is (c).

[0263] In some embodiments, for compounds of formula (I), (II), or their subformulas, ring B is (a), X1 is CH, and R A is methyl, Y 1 CR 3 Y 2 If is N, then ring A is further selected from methyl-substituted tetrahydrofuranyl. In some embodiments, ring B is (a), X1 is CH, and R A It is methyl, and Y 1 CR 3 Y 2 is N; ring A is further selected from methyl-substituted tetrahydrofuranyl.

[0264] In some embodiments, for compounds of formula (I), (II), or their subformulas, R A ga-OR 11 If that is the case, then R 5 is chloro. In some embodiments, R A is -OR 11 And; R 5 That is Chlorophyll.

[0265] Compounds of formulas (V) and (VI) Some embodiments include compounds of formula (V): [ka] or a pharmaceutically acceptable salt thereof (in the formula, Q 1 is N, S, O or CR 3 Q 2 is N or C, and Q 3 is N or CR 4 Q 4 is N or CR 3 Q 5 is C or N, and each [ka] Q 1 Q 2 Q3 Q 4 , and Q 5 The bicyclic ring system containing represents a single or double bond such that it becomes benzo[d]thiazole, benzo[d]xazole, imidazo[1,2-a]pyridine, thiazolo[5,4-b]pyridine, imidazo[1,2-b]pyridazine, pyrazolo[1,5-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, or [1,2,4]triazolo[1,5-b]pyridazine, R A is halogen, -OR 10 , -SR 10 , -N(R 10 )2, -CN, one or more halogens or -OR 10 C arbitrarily replaced by 1-6 Alkyl, C 3- Selected from C6 saturated cycloalkyls and 3- to 6-membered saturated heterocycloalkyls; Ring A is C3-C 10 Saturated cycloalkyl, C3-C 10 Selected from partially saturated carbocyclic rings, 3-10 member saturated heterocycloalkyl groups, and 3-10 member partially saturated heterocyclic rings, each of which is, Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R 11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R 11 -NO2, and =O; Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R 11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R 11 C is optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-OC(O)N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )S(O)2(R 11 ), -S(O)R 11 -S(O)2R 11 -S(O)2N(R 11 )2, -S(O)(NR 11 )R11 (Optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN) Optionally substituted with one or more substituents independently selected from; Ring B is C3-C 10 Selected from carbocyclic rings and 3- to 12-membered heterocycles, each of these is Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12-S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 C is optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 (Optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN) Optionally substituted with one or more substituents independently selected from; R 1 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and -C(O)R 13 Selected from; R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 ) Selected from -NO2 and -CN; R3 Independently, hydrogen, halogen, and C exist in each of their respective forms. 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 4 is hydrogen, halogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 10 , R 11 , R 12 , R 13 , and R 14 These are, independently, hydrogen and C in their respective existences. 1-4 Alkyl, C 1-4 Selected from haloalkyls and cycloalkyls optionally substituted with one or more halogens; n is selected from 0, 1, and 2; However, if ring B is pyrazolyl, then ring A is not N-Boc pyrrolidinyl. To provide.

[0266] In some embodiments, for a compound of formula (V), Q 1 CR 3 In some embodiments, Q 1 is N. In some embodiments, Q 1 is S. In some embodiments, Q 1 In some embodiments, Q 2 is C. In some embodiments, Q 2 is N. In some embodiments, Q 3 CR 4 In some embodiments, Q 3 is N. In some embodiments, Q 4 CR 3 In some embodiments, Q 4 is N. In some embodiments, Q 5 It is C.

[0267] In some embodiments, for a compound of formula (V), Q 1 Q2 Q 3 Q 4 , and Q 5 The bicyclic ring system containing Q is benzo[d]thiazole, benzo[d]oxazole, or thiazolo[5,4-b]pyridine. In some embodiments, Q 1 Q 2 Q 3 Q 4 , and Q 5 The bicyclic ring system containing is imidazo[1,2-a]pyridine, imidazo[1,2-b]pyridazine, or pyrazolo[1,5-a]pyridine. In some embodiments, Q 1 Q 2 Q 3 Q 4 , and Q 5 The bicyclic ring systems containing [1,2,4]triazolo[1,5-a]pyridine or [1,2,4]triazolo[1,5-b]pyridazine.

[0268] In some embodiments, for a compound of formula (V), Q 1 Q 2 Q 3 Q 4 , and Q 5 A bicyclic ring system containing is benzo[d]thiazole. In some embodiments, Q 1 Q 2 Q 3 Q 4 , and Q 5 A bicyclic ring system containing Q is a benzo[d]oxazole. In some embodiments, Q 1 Q 2 Q 3 Q 4 , and Q 5 The bicyclic ring system containing is imidazo[1,2-a]pyridine. In some embodiments, Q 1 Q 2 Q 3 Q 4 , and Q 5 The bicyclic ring system containing is thiazolo[5,4-b]pyridine. In some embodiments, Q 1 Q 2 Q 3 Q4 , and Q 5 The bicyclic ring system containing is imidazo[1,2-b]pyridazine. In some embodiments, Q 1 Q 2 Q 3 Q 4 , and Q 5 The bicyclic ring system containing is pyrazolo[1,5-a]pyridine. In some embodiments, Q 1 Q 2 Q 3 Q 4 , and Q 5 The bicyclic ring system containing is [1,2,4]triazolo[1,5-a]pyridine. In some embodiments, Q 1 Q 2 Q 3 Q 4 , and Q 5 The bicyclic ring system containing [1,2,4]triazolo[1,5-b]pyridazine is [1,2,4]triazolo[1,5-b]pyridazine.

[0269] Some embodiments involve compounds of formula (VA): [ka] or a pharmaceutically acceptable salt thereof is provided. In some embodiments, Q 3 CR 4 In some embodiments, Q 3 is N. In some embodiments, Q 4 CR 3 In some embodiments, Q 4 is N. In some embodiments, Q 3 CR 4 Q 4 is N. In some embodiments, Q 3 CR 4 Q 4 CR 3 In some embodiments, Q 3 is N and Q 4 CR 3 That is the case.

[0270] Some embodiments involve compounds of formula (VB): [ka] or a pharmaceutically acceptable salt thereof is provided. In some embodiments, Q 3 CR 4 In some embodiments, Q 3 It is N.

[0271] Some embodiments involve compounds of formula (VC): [ka] or a pharmaceutically acceptable salt thereof is provided. In some embodiments, Q 4 CR 3 In some embodiments, Q 4 It is N.

[0272] Some embodiments involve compounds of formula (VD): [ka] or a pharmaceutically acceptable salt thereof is provided. In some embodiments, Q 3 CR 4 In some embodiments, Q 3 It is N.

[0273] Some embodiments involve compounds of formula (VE): [ka] or a pharmaceutically acceptable salt thereof is provided. In some embodiments, Q 3 CR 4 In some embodiments, Q 3 It is N.

[0274] Some embodiments involve compounds of formula (VF): [ka] or a pharmaceutically acceptable salt thereof is provided.

[0275] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), or (VF), R 1 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and -C(O)R 13 Selected from; R 13 C 1-4 Selected from alkyl and cycloalkyl. In some embodiments, R 1 is hydrogen and C 1-4 Selected from alkyl groups. In some embodiments, R 1 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and -C(O)R 13 Selected from; R 13 C 1-4 Selected from alkyl and cyclopropyl optionally substituted with one or more -F. In some embodiments, R 1 is hydrogen, C 1-4 Alkyl and C 1-4 Selected from haloalkyls. In some embodiments, R 1 is hydrogen and C 1-4 Selected from alkyl groups. In some embodiments, R 1 These are hydrogen, -CH3, -CF3, and [ka] Selected from. In some embodiments, R 1 It is hydrogen.

[0276] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), or (VF), R 2 Independently, in each presence, halogen, C 1-4 Alkyl, C 1-4 Selected from haloalkyl and -CN. In some embodiments, R 2is independently selected from halogen and C 1-4 alkyl in each occurrence.

[0277] In some embodiments, for a compound of formula (V), (VA), (VB), (VC), (VD), (VE), or (VF), R 3 is independently selected from hydrogen, halogen, and C 1-4 alkyl in each occurrence. In some embodiments, R 3 is independently selected from hydrogen and C 1-4 alkyl in each occurrence. In some embodiments, each R 3 is independently hydrogen.

[0278] In some embodiments, for a compound of formula (V), (VA), (VB), (VC), (VD), (VE), or (VF), R 4 is selected from hydrogen, halogen, and C 1-4 alkyl. In some embodiments, R 4 is selected from hydrogen and C 1-4 alkyl. R 4 is selected from hydrogen and -CH3. In some embodiments, R 4 is hydrogen.

[0279] In some embodiments, for a compound of formula (V), (VA), (VB), (VC), (VD), (VE), or (VF), n is 0 or 1. In some embodiments, n is 0.

[0280] Some embodiments are compounds of formula (VI):

Chemical formula

[0281] For the purpose of clarification, if ring A is substituted with one or more substituents, then one or more substituents are R A It does not include the base, but exists in addition to it.

[0282] In some embodiments, if a site or list of sites is optionally replaced by one or more substituents, the one or more substituents are 1 to 4 substituents (e.g., 1 to 3, 2 to 4, 2 to 3, 1 to 2, 3 to 4, 1, 2, 3, or 4 substituents). For example, in some embodiments, the one or more substituents are 1 to 4 substituents. In some embodiments, the one or more substituents are 1 substituent.

[0283] In some embodiments, for a compound of formula (VI), Q 1 CR 3 Q 2 is N. In some embodiments, Q 1 CR 3 Q 2 is N and Q 3 is N. In some embodiments, Q 1 CR 3 Q 2 is N and Q 3 CR 4In some embodiments, Q 1 CR 3 Q 2 is N and Q 3 is CH. In some embodiments, Q 1 S is Q 2 is C. In some embodiments, Q 1 is S; Q 2 is C; Q 3 is N. In some embodiments, Q 1 is S; Q 2 is C; Q 3 CR 4 In some embodiments, Q 1 is S; Q 2 is C; Q 3 is CH. In some embodiments, Q 3 is N. In some embodiments, Q 3 CR 4 In some embodiments, Q 3 CR 4 And; R 4 R is selected from hydrogen and halogen. In some embodiments, 4 is hydrogen and C 1-4 Selected from alkyl groups. In some embodiments, R 4 Q is selected from hydrogen and -CH3. In some embodiments, Q 3 is CH. In some embodiments, Q 4 is CR3. In some embodiments, Q 4 is N. In some embodiments, Q 4 CR 3 And R 3 R is selected from hydrogen and halogen. In some embodiments, 3 is hydrogen and C 1-4 Selected from alkyl groups. In some embodiments, R 3 Q is selected from hydrogen and -CH3. In some embodiments, Q 4 It is CH.

[0284] In some embodiments, for a compound of formula (VI), Q 1 CR 3 Q 2 is N and Q 3 is N and Q 4 CR 3 In some embodiments, Q 1 CR 3 Q 2 is N and Q 3 CR 4 Q 4 CR 3 In some embodiments, Q 1 CR 3 Q 2 is N and Q 3 CR 4 Q 4 CR 3 In some embodiments, Q 1 CR 3 Q 2 is N and Q 3 CR 4 Q 4 is N. In some embodiments, Q 1 CH is Q 2 is N and Q 3 CH is Q 4 It is N.

[0285] In some embodiments, the compound is of formula (VIA): [ka] or a pharmaceutically acceptable salt thereof.

[0286] In some embodiments, the compound is of formula (VIA-1): [ka] or a pharmaceutically acceptable salt thereof.

[0287] In some embodiments, the compound is of formula (VIB):

Chemical formula

[0288] In some embodiments, the compound is of formula (VIC):

Chemical formula

[0289] In some embodiments, the compound is of formula (VIC-1):

Chemical formula

[0290] In some embodiments, the compound is of formula (VIC-2):

Chemical formula

[0291] In some embodiments, for the compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), R 1 is selected from hydrogen, C 1-4 alkyl, and -C(O)R 13 . In some embodiments, R 1 is selected from hydrogen and C 1-4 alkyl. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 is C 1-4 alkyl. In some embodiments, R 1 is -C(O)R 13 . In some embodiments, R 1These are hydrogen, -CH3, and [ka] Selected from.

[0292] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), n is 0 or 1. In some embodiments, n is 1 or 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2.

[0293] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), R 2 Independently, halogens and C in each presence 1-4 Selected from alkyl. In some embodiments, R 2 is a halogen. In some embodiments, R 2 C 1-4 It is alkyl. In some embodiments, R 2 C 1-4 In some embodiments, R 2 is -OR 14 In some embodiments, R 2 -SR 14 In some embodiments, R 2 is -N(R 14 )2. In some embodiments, R 2 It is NO2. In some embodiments, R 2 It is -CN.

[0294] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), R 3 is hydrogen. In some embodiments, R 3 is a halogen. In some embodiments, R 3 is fluoro. In some embodiments, R 3 is chloro. In some embodiments, R 3 C 1-4 It is alkyl. In some embodiments, R 3 is methyl. In some embodiments, R 3 C 1-4 In some embodiments, R 3 It is trifluoromethyl.

[0295] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), R 2 Independently, halogens and C in each presence 1-4 Selected from alkyl. In some embodiments, R 2 is a halogen. In some embodiments, R 2 C 1-4 It is alkyl. In some embodiments, R 2 C 1-4 In some embodiments, R 2 is -OR 14 In some embodiments, R 2 -SR 14 In some embodiments, R 2 is -N(R 14 )2. In some embodiments, R 2 It is NO2. In some embodiments, R 2 It is -CN.

[0296] In some embodiments, the compound is of formula (VIA-2): [ka] or a pharmaceutically acceptable salt thereof.

[0297] In some embodiments, the compound is of formula (VIA-3): [ka] or a pharmaceutically acceptable salt thereof.

[0298] In some embodiments, the compound is of formula (VIB-1): [ka] or a pharmaceutically acceptable salt thereof.

[0299] In some embodiments, the compound is of formula (VIB-2): [ka] or a pharmaceutically acceptable salt thereof.

[0300] In some embodiments, the compound is of formula (VIC-3): [ka] or a pharmaceutically acceptable salt thereof.

[0301] In some embodiments, the compound is of formula (VID-1): [ka] or a pharmaceutically acceptable salt thereof.

[0302] In some embodiments, the compound is of formula (ID-2): [ka] or a pharmaceutically acceptable salt thereof.

[0303] In some embodiments, the compound is of formula (VIE-1): [ka] or a pharmaceutically acceptable salt thereof.

[0304] In some embodiments, the compound is of formula (VIE-2): [ka] or a pharmaceutically acceptable salt thereof.

[0305] In some embodiments, the compound is of formula (VIF): [ka] or a pharmaceutically acceptable salt thereof.

[0306] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is C3-C 10 Selected from carbocyclic rings and 3- to 12-membered heterocycles, each of these is Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )2, =O, -CN, optionally substituted with one or more substituents independently selected from C 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 (Optionally substituted with one or more substituents independently selected from ,=O, and -CN) It is optionally substituted with one or more substituents selected independently of it.

[0307] In some embodiments, for compounds of formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), the heterocycle of ring B contains 1 to 4 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring B contains 1 to 3 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring B contains 1 to 2 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring B contains 2 to 3 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring B contains 1 heteroatom independently selected from O, N, and S. In some embodiments, the heterocycle of ring B contains 2 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring B contains 3 heteroatoms independently selected from O, N, and S. In some embodiments, the heterocycle of ring B contains 4 heteroatoms independently selected from O, N, and S.

[0308] In some embodiments, for compounds of formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), the heterocycle of ring B contains 1 to 4 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring B contains 1 to 3 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring B contains 1 to 2 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring B contains 2 to 3 heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring B contains one heteroatom selected from O and N. In some embodiments, the heterocycle of ring B contains two heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring B contains three heteroatoms independently selected from O and N. In some embodiments, the heterocycle of ring B contains four heteroatoms independently selected from O and N.

[0309] In some embodiments, for compounds of formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), the heterocycle of ring B contains four N heteroatoms. In some embodiments, the heterocycle of ring B contains three N heteroatoms. In some embodiments, the heterocycle of ring B contains three N heteroatoms and one O heteroatom. In some embodiments, the heterocycle of ring B contains two N heteroatoms and one O heteroatom. In some embodiments, the heterocycle of ring B contains two N heteroatoms and one S heteroatom. In some embodiments, the heterocycle of ring B contains one O heteroatom and one N heteroatom. In some embodiments, the heterocycle of ring B contains one O heteroatom and one S heteroatom. In some embodiments, the heterocycle of ring B contains one S heteroatom and one N heteroatom. In some embodiments, the heterocycle of ring B contains two N heteroatoms. In some embodiments, the heterocycle of ring B contains one heteroatom that is O. In some embodiments, the heterocycle of ring B contains one heteroatom that is N. In some embodiments, the heterocycle of ring B contains one heteroatom that is S.

[0310] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-C(O)N(R 12 )2, -N(R12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )2, =O, -CN, optionally substituted with one or more substituents independently selected from C 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 (Optionally substituted with one or more substituents independently selected from ,=O, and -CN) C3-C optionally substituted with one or more substituents independently selected from 10 It is a carbon ring.

[0311] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )2, =O, -CN, optionally substituted with one or more substituents independently selected from C 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 (Optionally substituted with one or more substituents independently selected from ,=O, and -CN) It is a 3- to 12-membered heterocycle optionally substituted with one or more substituents independently selected from the parentheses.

[0312] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is C3-C 10 Selected from carbocyclic rings and 3- to 12-membered heterocycles, each of these is Halogen, -OR 12 , -SR 12, -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )2, =O, -CN, and C, which are optionally substituted with 1 to 4 substituents independently selected from these. 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 (Optionally substituted with 1 to 4 substituents independently selected from ,=O, and -CN) It is optionally substituted with 1 to 4 substituents independently selected from the given molecule.

[0313] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is C6-C 10Selected from aryls and 3- to 12-membered heteroaryls, each of these is Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )2, =O, and C optionally substituted with one or more substituents independently selected from -CN 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 (Optionally substituted with one or more substituents independently selected from ,=O, and -CN) It is optionally substituted with one or more substituents selected independently of it.

[0314] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is C6-C 10 Selected from aryls and 3- to 12-membered heteroaryls, each of these is Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 -NO2, =O, and -CN; Halogen, -OR 12 , -SR 12 , -N(R 12 )C optionally substituted with 1 to 4 substituents independently selected from 2, =O, and -CN 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 (Optionally substituted with 1 to 4 substituents independently selected from ,=O, and -CN) It is optionally substituted with 1 to 4 substituents independently selected from the given molecule.

[0315] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is C6-C 10 Selected from aryls and 3- to 12-membered heteroaryls, each of which is a halogen, -OR 12 , -N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 , =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterocycles, as well as halogens and -OR 12 C optionally substituted with one or more substituents independently selected from 1-6 It is optionally substituted with one or more substituents independently selected from the alkyl group. In some embodiments, ring B is C6-C 10 Selected from aryls and 3- to 12-membered heteroaryls, each of which is a halogen, -OR 12 , -N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 , =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterocycles, as well as halogens and -OR12 C optionally substituted with one or more substituents independently selected from 1-6 Optionally substituted with one or more substituents independently selected from alkyl; R 12 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl and C 3-6 Selected from cycloalkyl groups.

[0316] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is C6-C 10 Selected from aryls and 3- to 12-membered heteroaryls, each of which is a halogen, -OR 12 , -N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 , =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterocycles, as well as halogens and -OR 12 C optionally substituted with one or more substituents independently selected from 1-6 Optionally substituted with one or more substituents independently selected from alkyl; R 12 The ring is selected from hydrogen, -CH3, -CH2CH2CH3, -CH2CH(CH3)2, -CH2CF3, and cyclopropyl. In some embodiments, ring B is C6-C 10 Selected from aryls and 3- to 12-membered heteroaryls, each of which is a halogen, -OR 12 , -N(R 12 )2, -C(O)N(R12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 , =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterocycles, as well as halogens and -OR 12 C optionally substituted with one or more substituents independently selected from 1-6 It is optionally substituted with one or more substituents independently selected from the alkyl group.

[0317] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is C6-C 10 Selected from aryls and 3- to 12-membered heteroaryls, each of which is a halogen, -OR 12 , -N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 , =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterocycles, as well as halogens and -OR 12 C is optionally substituted with 1 to 4 substituents independently selected from the above. 1-6The ring B is optionally substituted with 1 to 4 substituents independently selected from the alkyl group. In some embodiments, ring B is selected from phenyl, pyridinyl, pyridadinyl, pyrimidinyl, benzthiazolyl, benzimidazolyl, and benzflazanyl, each of which is a halogen, -OR 12 , -N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 , =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterocycles, as well as halogens and -OR 12 C optionally substituted with one or more substituents independently selected from 1-6 It is optionally substituted with one or more substituents independently selected from alkyl. In some embodiments, ring B is not pyrazolyl. In some embodiments, ring B is selected from phenyl, pyridinyl, pyridadinyl, pyrimidinyl, benzthiazolyl, benzimidazolyl, and benzflazanyl, each of which is halogen, -OR 12 , -N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 , =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterocycles, as well as halogens and -OR 12 C is optionally substituted with 1 to 4 substituents independently selected from the above. 1-6 It is optionally substituted with 1 to 4 substituents independently selected from the alkyl group.

[0318] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is phenyl, pyridinyl, pyridazinyl, pyrim Dinyl, indolyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, 2,1,3-benzoxadiazolylbenzflazanyl, thiazolo[4,5-b]pyridinyl, pyrrolo[2,3-b]pyridinyl, imidazo[1,5-a]pyridinyl, quinolinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl, each of which is selected from -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] It is optionally substituted with one or more substituents independently selected from the ring. In some embodiments, ring B is selected from phenyl, pyridinyl, pyridadinyl, pyrimidinyl, benzthiazolyl, benzimidazolyl, and benzflazanyl, each of which is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] It is optionally substituted with one or more substituents selected independently of it.

[0319] In some embodiments, ring B is selected from phenyl, pyridinyl, pyridadinyl, pyrimidinyl, benzthiazolyl, benzimidazolyl, and benzflazanyl, each of which is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] It is optionally substituted with 1 to 4 substituents independently selected from the given molecule.

[0320] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] Phenyl is optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring B is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] A pyridinyl ring optionally substituted with 1 to 4 substituents independently selected from the ring. In some embodiments, ring B is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] Pyridazinyl is optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring B is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] A pyrimidinyl optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring B is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] The benzthiazolyl is optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring B is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] The benzimidazolyl is optionally substituted with 1 to 4 substituents independently selected from the above. In some embodiments, ring B is -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, [ka] It is benzflazanyl optionally substituted with 1 to 4 substituents independently selected from the above.

[0321] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is [ka] [ka] Selected from.

[0322] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] is. In some embodiments, ring B is

Chemical formula

[0323] In some embodiments, for the compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is selected from (a), (b), and (c): (a)

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0324] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 1 or 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2.

[0325] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), q is 0, 1, or 2. In some embodiments, q is 0 or 1. In some embodiments, q is 1 or 2. In some embodiments, q is 0. In some embodiments, p is 1. In some embodiments, q is 2.

[0326] In some embodiments, for compounds of formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), r is 0, 1, or 2. In some embodiments, r is 0 or 1. In some embodiments, r is 1 or 2. In some embodiments, r is 0. In some embodiments, r is 1. In some embodiments, r is 2.

[0327] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), X 1 In some embodiments, X 1 is CH. In some embodiments, X 1 is CH. In some embodiments, X 2 In some embodiments, X2 , NR 7 In some embodiments, X 2 is NH. In some embodiments, X 3 In some embodiments, X 3 In some embodiments, X 3 is NH. In some embodiments, X 4 In some embodiments, X 4 CR 9 That is the case.

[0328] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), X 3 S is X 4 In some embodiments, X 3 S is X 4 CR 9 In some embodiments, X 3 is N and X 4 In some embodiments, X 3 N is X 4 CR 9 In some embodiments, X 3 NH and X 4 In some embodiments, X 3 NH and X 4 CR 9 That is the case.

[0329] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 9 is hydrogen. In some embodiments, R 9 C 1-4 It is alkyl. In some embodiments, R 9 It is methyl.

[0330] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] That is the case.

[0331] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R B is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 Selected from -NO2, =O, and -CN. In some embodiments, R B is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 Selected from , =O, and -CN. In some embodiments, R B is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -OR 12 Selected from. In some embodiments, R B is halogen, methyl, C 1-6 Haloalkyl and -OR 12 Selected from. In some embodiments, R B is a halogen. In some embodiments, R B C 1-4 It is alkyl. In some embodiments, R B is methyl. In some embodiments, R B C 1-4 In some embodiments, R B is -OR 12 In some embodiments, R B -SR 12 In some embodiments, R B is -N(R 12 )2. In some embodiments, R B is -C(O)R 12 In some embodiments, R B is -C(O)OR 12 In some embodiments, R B is -OC(O)R 12 In some embodiments, R B is -C(O)N(R 12 )2. In some embodiments, R B is -N(R 12 )C(O)R 12 In some embodiments, R B is -N(R 12 )S(O)2(R 12 ) is. In some embodiments, RB is -S(O)2R 12 In some embodiments, R B is -S(O)2N(R 12 )2. In some embodiments, R B is -NO2. In some embodiments, R B It is -CN.

[0332] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is [ka] (In the formula, X 1 These are N, CH, and CR 5 (Selected from)

[0333] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is [ka] X 2 S and NR 7 Selected from.

[0334] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), ring B is [ka] X 3 It is selected from S, N, and NH, and X 4 O and CR 9 Selected from, X 5 is N or CH, and X 6 is N or CH, and each [ka] The single or double bonds represent ring B such that it forms an aromatic bicyclic ring system.

[0335] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 7 and R 9 These are hydrogen and C, respectively. 1-4 Selected independently of alkyl. In some embodiments, R 7 is hydrogen. In some embodiments, R 7 C 1-4 It is alkyl. In some embodiments, R 7 C 1-4 In some embodiments, R 9 is hydrogen. In some embodiments, R 9 C 1-4It is alkyl. In some embodiments, R 9 C 1-4 It is a haloalkyl group.

[0336] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 6 and R 8 These are, independently, halogens and C in their respective presences. 1-4 Selected from alkyl groups.

[0337] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 5 Independently, halogens and C in each presence 1-4 Selected from alkyl groups. In some embodiments, R 5 is a halogen. In some embodiments, R 5 C 1-4 It is alkyl. In some embodiments, R 5 C 1-4 In some embodiments, R 5 is -OR 12 In some embodiments, R 5 -SR 12 In some embodiments, R 5 is -N(R 12 )2. In some embodiments, R 5 is -C(O)R 12 In some embodiments, R 5is -C(O)OR 12 In some embodiments, R 5 is -OC(O)R 12 In some embodiments, R 5 is -C(O)N(R 12 )2. In some embodiments, R 5 is -N(R 12 )C(O)R 12 In some embodiments, R 5 is -N(R 12 )S(O)2(R 12 ) is. In some embodiments, R 5 is -S(O)2R 12 In some embodiments, R 5 is -S(O)2N(R 12 )2. In some embodiments, R 5 is -NO2. In some embodiments, R 5 It is -CN.

[0338] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 6 is a halogen. In some embodiments, R 6 C 1-4 It is alkyl. In some embodiments, R 6 C 1-4 In some embodiments, R 6 is -OR 12 In some embodiments, R 6 -SR 12 In some embodiments, R 6 is -N(R 12 )2. In some embodiments, R 6 is -C(O)R 12In some embodiments, R 6 is -C(O)OR 12 In some embodiments, R 6 is -OC(O)R 12 In some embodiments, R 6 is -C(O)N(R 12 )2. In some embodiments, R 6 is -N(R 12 )C(O)R 12 In some embodiments, R 6 is -N(R 12 )S(O)2(R 12 ) is. In some embodiments, R 6 is -S(O)2R 12 In some embodiments, R 6 is -S(O)2N(R 12 )2. In some embodiments, R 6 is -NO2. In some embodiments, R 6 It is -CN.

[0339] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 8 is a halogen. In some embodiments, R 8 C 1-4 It is alkyl. In some embodiments, R 8 C 1-4 In some embodiments, R 8 is -OR 12 In some embodiments, R 8 -SR 12 In some embodiments, R 8 is -N(R 12 )2. In some embodiments, R 8is -C(O)R 12 In some embodiments, R 8 is -C(O)OR 12 In some embodiments, R 8 is -OC(O)R 12 In some embodiments, R 8 is -C(O)N(R 12 )2. In some embodiments, R 8 is -N(R 12 )C(O)R 12 In some embodiments, R 8 is -N(R 12 )S(O)2(R 12 ) is. In some embodiments, R 8 is -S(O)2R 12 In some embodiments, R 8 is -S(O)2N(R 12 )2. In some embodiments, R 8 is -NO2. In some embodiments, R 8 It is -CN.

[0340] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 10 is hydrogen. In some embodiments, R 10 C 1-6 It is alkyl. In some embodiments, R 10 C 1-4 In some embodiments, R 10 is a cycloalkyl group optionally substituted with one or more halogens. In some embodiments, R 10 is hydrogen. In some embodiments, R 10 C 1-6 It is alkyl. In some embodiments, R10 C 1-4 In some embodiments, R 10 These are cycloalkyl groups optionally substituted with 1 to 4 halogens.

[0341] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 11 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 11 is hydrogen. In some embodiments, R 11 C 1-6 It is alkyl. In some embodiments, R 11 C 1-4 In some embodiments, R 11 is a cycloalkyl group optionally substituted with one or more halogens. In some embodiments, R 11 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups. In some embodiments, R 11 is hydrogen. In some embodiments, R 11 C 1-6 It is alkyl. In some embodiments, R 11 C 1-4 In some embodiments, R 11 These are cycloalkyl groups optionally substituted with 1 to 4 halogens.

[0342] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 12 is hydrogen. In some embodiments, R 12 C 1-6 It is alkyl. In some embodiments, R 12 C 1-4 In some embodiments, R 12 is a cycloalkyl group optionally substituted with one or more halogens. In some embodiments, R 12 is -CH3. In some embodiments, R 12 This is CH2CF3. In some embodiments, R 12 is cyclopropyl. In some embodiments, R 12 R is independently selected from hydrogen, -CH3, -CH2CH2CH3, -CH2CH(CH3)2, -CH2CF3, and cyclopropyl in each presence. In some embodiments, R 12 is hydrogen. In some embodiments, R 12 C 1-6 It is alkyl. In some embodiments, R 12 C 1-4 In some embodiments, R 12 is a cycloalkyl group optionally substituted with 1 to 4 halogens. In some embodiments, R 12 is -CH3. In some embodiments, R 12 This is CH2CF3. In some embodiments, R 12 It is cyclopropyl.

[0343] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 13 C 1-4 Selected from alkyl and cyclopropyl optionally substituted with one or more -F. In some embodiments, R 13 is hydrogen. In some embodiments, R 13 C 1-6 It is alkyl. In some embodiments, R 13 C 1-4 In some embodiments, R 13 This is a cycloalkyl group optionally substituted with one or more halogens.

[0344] In some embodiments, for compounds of formula (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC-3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R 14 is hydrogen. In some embodiments, R 14 C 1-6 It is alkyl. In some embodiments, R 14 C 1-4 In some embodiments, R 14 This is a cycloalkyl group optionally substituted with one or more halogens.

[0345] In some embodiments, the compound is of formula (VIA-4): [ka] or a pharmaceutically acceptable salt thereof (wherein X1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0346] In some embodiments, the compound is of formula (VIA-5): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from)

[0347] In some embodiments, the compound is of formula (VIA-6): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0348] In some embodiments, the compound is of formula (VIA-7): [ka] or a pharmaceutically acceptable salt thereof.

[0349] In some embodiments, the compound is of formula (VIB-3): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X1 It is CH.

[0350] In some embodiments, the compound is of formula (VIC-4): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0351] In some embodiments, the compound is of formula (VID-3): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0352] In some embodiments, the compound is of formula (VID-4): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0353] In some embodiments, for compounds of formula (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIB-3), (VIC-4), (VID-3), or (VID-4), R 5 Independently, halogens and C in each presence1-4 Selected from alkyl groups. In some embodiments, R 5 is a halogen. In some embodiments, R 5 C 1-4 It is alkyl. In some embodiments, R 5 C 1-4 In some embodiments, R 5 is -OR 12 In some embodiments, R 5 -SR 12 In some embodiments, R 5 is -N(R 12 )2. In some embodiments, R 5 is -C(O)R 12 In some embodiments, R 5 is -C(O)OR 12 In some embodiments, R 5 is -OC(O)R 12 In some embodiments, R 5 is -C(O)N(R 12 )2. In some embodiments, R 5 is -N(R 12 )C(O)R 12 In some embodiments, R 5 is -N(R 12 )S(O)2(R 12 ) is. In some embodiments, R 5 is -S(O)2R 12 In some embodiments, R 5 is -S(O)2N(R 12 )2. In some embodiments, R 5 is -NO2. In some embodiments, R 5 It is -CN.

[0354] In some embodiments, for compounds of formula (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIB-3), (VIC-4), (VID-3), or (VID-4), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 1 or 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2.

[0355] In some embodiments, the compound is of formula (VIC-5): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0356] In some embodiments, the compound is of formula (VIA-8): [ka] or a pharmaceutically acceptable salt thereof.

[0357] In some embodiments, for compounds of formula (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB-3), (VIC-4), (VIC-5), (VID-3), or (VID-4), R B is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-OC(O)N(R 12 )2, -C(O)N(R12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )2, -N(R 12 )S(O)2(R 12 ), -S(O)R 12 -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 Selected from -NO2, =O, and -CN. In some embodiments, R B is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 12 , -N(R 12 )2, -C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2(R 12 ), -S(O)2R 12 -S(O)2N(R 12 )2, -S(O)(NR 12 )R 12 Selected from , =O, and -CN. In some embodiments, R B is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -OR 12 Selected from. In some embodiments, R B is halogen, methyl, C 1-6 Haloalkyl and -OR 12 Selected from. In some embodiments, R B is a halogen. In some embodiments, R B C 1-4 It is alkyl. In some embodiments, R B is methyl. In some embodiments, R B C 1-4 In some embodiments, R B is -OR12 In some embodiments, R B -SR 12 In some embodiments, R B is -N(R 12 )2. In some embodiments, R B is -C(O)R 12 In some embodiments, R B is -C(O)OR 12 In some embodiments, R B is -OC(O)R 12 In some embodiments, R B is -C(O)N(R 12 )2. In some embodiments, R B is -N(R 12 )C(O)R 12 In some embodiments, R B is -N(R 12 )S(O)2(R 12 ) is. In some embodiments, R B is -S(O)2R 12 In some embodiments, R B is -S(O)2N(R 12 )2. In some embodiments, R B is -NO2. In some embodiments, R B It is -CN.

[0358] In some embodiments, the compound is of formula (VIC-6): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0359] In some embodiments, the compound is of formula (VIC-7): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0360] In some embodiments, the compound is of formula (VID-5): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0361] In some embodiments, the compound is of formula (VID-6): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0362] In some embodiments, the compound is of formula (VIE-3): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1It is CH.

[0363] In some embodiments, the compound is of formula (VIE-4): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0364] In some embodiments, the compound is of formula (VIE-5): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0365] In some embodiments, the compound is of formula (VIE-6): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0366] In some embodiments, the compound is of formula (VIF-1): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0367] In some embodiments, the compound is of formula (VIF-2): [ka] or a pharmaceutically acceptable salt thereof (wherein X 1 These are N, CH, and CR 5 (Selected from) In some embodiments, X 1 In some embodiments, X 1 It is CH.

[0368] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VI A-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), For the compounds (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the saturated heterocycloalkyl of ring A contains 1 to 4 heteroatoms independently selected from O, N, and S. In some embodiments, the saturated heterocycloalkyl of ring A contains 1 to 3 heteroatoms independently selected from O, N, and S. In some embodiments, the saturated heterocycloalkyl of ring A contains 1 to 2 heteroatoms independently selected from O, N, and S. In some embodiments, the saturated heterocycloalkyl of ring A contains 2 to 3 heteroatoms independently selected from O, N, and S. In some embodiments, the saturated heterocycloalkyl ring A contains one heteroatom selected from O, N, and S. In some embodiments, the saturated heterocycloalkyl ring A contains two heteroatoms independently selected from O, N, and S. In some embodiments, the saturated heterocycloalkyl ring A contains three heteroatoms independently selected from O, N, and S. In some embodiments, the saturated heterocycloalkyl ring A contains four heteroatoms independently selected from O, N, and S.

[0369] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VI A-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5) For the compounds (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the saturated heterocycloalkyl of ring A contains 1 to 4 heteroatoms independently selected from O and N. In some embodiments, the saturated heterocycloalkyl of ring A contains 1 to 3 heteroatoms independently selected from O and N. In some embodiments, the saturated heterocycloalkyl of ring A contains 1 to 2 heteroatoms independently selected from O and N. In some embodiments, the saturated heterocycloalkyl of ring A contains 2 to 3 heteroatoms independently selected from O and N. In some embodiments, the saturated heterocycloalkyl ring A contains one heteroatom selected from O and N. In some embodiments, the saturated heterocycloalkyl ring A contains two heteroatoms independently selected from O and N. In some embodiments, the saturated heterocycloalkyl ring A contains three heteroatoms independently selected from O and N. In some embodiments, the saturated heterocycloalkyl ring A contains four heteroatoms independently selected from O and N.

[0370] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5) , (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4) For the compounds (VIC-5), (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the saturated heterocycloalkyl ring A contains 4 N heteroatoms. In some embodiments, the saturated heterocycloalkyl ring A contains 3 N heteroatoms. In some embodiments, the saturated heterocycloalkyl ring A contains 3 N heteroatoms and 1 O heteroatom. In some embodiments, the saturated heterocycloalkyl ring A contains 2 N heteroatoms and 1 O heteroatom. In some embodiments, the saturated heterocycloalkyl ring A contains 2 N heteroatoms and 1 S heteroatom. In some embodiments, the saturated heterocycloalkyl ring A contains one oxygen heteroatom and one nitrogen heteroatom. In some embodiments, the saturated heterocycloalkyl ring A contains one oxygen heteroatom and one sulfur heteroatom. In some embodiments, the saturated heterocycloalkyl ring A contains one sulfur heteroatom and one nitrogen heteroatom. In some embodiments, the saturated heterocycloalkyl ring A contains two nitrogen heteroatoms. In some embodiments, the saturated heterocycloalkyl ring A contains one oxygen heteroatom. In some embodiments, the saturated heterocycloalkyl ring A contains one nitrogen heteroatom. In some embodiments, the saturated heterocycloalkyl ring A contains one sulfur heteroatom.

[0371] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (V IA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5 For compounds of (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the partially saturated heterocycle of ring A contains 1 to 4 heteroatoms independently selected from O, N, and S. In some embodiments, the partially saturated heterocycle of ring A contains 1 to 3 heteroatoms independently selected from O, N, and S. In some embodiments, the partially saturated heterocycle of ring A contains 1 to 2 heteroatoms independently selected from O, N, and S. In some embodiments, the partially saturated heterocycle of ring A contains 2 to 3 heteroatoms independently selected from O, N, and S. In some embodiments, the partially saturated heterocycle of ring A contains one heteroatom selected from O, N, and S. In some embodiments, the partially saturated heterocycle of ring A contains two heteroatoms independently selected from O, N, and S. In some embodiments, the partially saturated heterocycle of ring A contains three heteroatoms independently selected from O, N, and S. In some embodiments, the partially saturated heterocycle of ring A contains four heteroatoms independently selected from O, N, and S.

[0372] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (V IA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC- For compounds of 5), (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the partially saturated heterocycle of ring A contains 1 to 4 heteroatoms independently selected from O and N. In some embodiments, the partially saturated heterocycle of ring A contains 1 to 3 heteroatoms independently selected from O and N. In some embodiments, the partially saturated heterocycle of ring A contains 1 to 2 heteroatoms independently selected from O and N. In some embodiments, the partially saturated heterocycle of ring A contains 2 to 3 heteroatoms independently selected from O and N. In some embodiments, the partially saturated heterocycle of ring A contains one heteroatom selected from O and N. In some embodiments, the partially saturated heterocycle of ring A contains two heteroatoms independently selected from O and N. In some embodiments, the partially saturated heterocycle of ring A contains three heteroatoms independently selected from O and N. In some embodiments, the partially saturated heterocycle of ring A contains four heteroatoms independently selected from O and N.

[0373] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5 ), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC- For compounds 4), (VIC-5), (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the partially saturated heterocycle of ring A contains 4 N heteroatoms. In some embodiments, the partially saturated heterocycle of ring A contains 3 N heteroatoms. In some embodiments, the partially saturated heterocycle of ring A contains 3 N heteroatoms and 1 O heteroatom. In some embodiments, the partially saturated heterocycle of ring A contains 2 N heteroatoms and 1 O heteroatom. In some embodiments, the partially saturated heterocycle of ring A contains two N heteroatoms and one S heteroatom. In some embodiments, the partially saturated heterocycle of ring A contains one O heteroatom and one N heteroatom. In some embodiments, the partially saturated heterocycle of ring A contains one O heteroatom and one S heteroatom. In some embodiments, the partially saturated heterocycle of ring A contains one S heteroatom and one N heteroatom. In some embodiments, the partially saturated heterocycle of ring A contains two N heteroatoms. In some embodiments, the partially saturated heterocycle of ring A contains one heteroatom that is O. In some embodiments, the partially saturated heterocycle of ring A contains one heteroatom that is N. In some embodiments, the partially saturated heterocycle of ring A contains one heteroatom that is S.

[0374] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), ( VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC -3), (VIC-4), (VIC-5), (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (V For the compounds IE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), ring A is C3-C 10 Selected from saturated cycloalkyls and 3- to 10-membered saturated heterocycloalkyls, each of which is, Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-C(O)N(R 11 )2, -N(R 11 )C(O)R 11 -NO2, and =O; Halogen, -OR 11 , -SR 11 , -N(R 11 )2, and C optionally substituted with one or more substituents independently selected from =O, -CN 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, -OR 11 , -SR 11 , -N(R 11 )2, C 1-6 Alkyl, C 1-6 (Optionally substituted with one or more substituents independently selected from haloalkyl, =O, and -CN) It is optionally substituted with one or more substituents selected independently of it.

[0375] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), ( VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC -3), (VIC-4), (VIC-5), (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (V For the compounds IE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), ring A is C3-C 10 Selected from saturated cycloalkyls and 3- to 10-membered saturated heterocycloalkyls, each of which is, Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-C(O)N(R 11 )2, -N(R 11 )C(O)R 11 -NO2, and =O; Halogen, -OR 11 , -SR 11 , -N(R 11 )2, and C optionally substituted with 1 to 4 substituents independently selected from =O and -CN 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, -OR 11 , -SR 11 , -N(R 11 )2, C 1-6 Alkyl, C 1-6 (Optionally substituted with 1 to 4 substituents independently selected from haloalkyl, =O, and -CN.) It is optionally substituted with 1 to 4 substituents independently selected from the given molecule.

[0376] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (V For compounds IC-3), (VIC-4), (VIC-5), (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), ring A is: Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-C(O)N(R 11 )2, -N(R 11 )C(O)R 11 -NO2, and =O; Halogen, -OR 11 , -SR 11 , -N(R 11 )2, and C optionally substituted with 1 to 4 substituents independently selected from =O and -CN 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, -OR 11 , -SR 11 , -N(R 11 )2, C 1-6 Alkyl, C 1-6 (Optionally substituted with 1 to 4 substituents independently selected from haloalkyl, =O, and -CN.) C3-C molecules optionally substituted with 1 to 4 substituents independently selected from the above. 10 It is a saturated cycloalkyl group.

[0377] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (V For compounds IC-3), (VIC-4), (VIC-5), (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), ring A is: Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)OR 11 ,-C(O)N(R 11 )2, -N(R 11 )C(O)R 11 -NO2, and =O; Halogen, -OR 11 , -SR 11 , -N(R 11 )2, and C optionally substituted with 1 to 4 substituents independently selected from =O and -CN 1-6 alkyl; and C 3-6 Carbon rings and 3- to 6-membered heterocycles (each of these being halogens, -OR 11 , -SR 11 , -N(R 11 )2, C 1-6 Alkyl, C 1-6 (Optionally substituted with 1 to 4 substituents independently selected from haloalkyl, =O, and -CN.) It is a 3- to 10-membered saturated heterocycloalkyl group, optionally substituted with 1 to 4 substituents independently selected from the given group.

[0378] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6) , (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), For the compounds (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), ring A is selected from C3-C6 saturated cycloalkyl and 3-6 member saturated heterocycloalkyl, each of which is a halogen, -C(O)OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl and one or more C 1-6 The ring A is optionally substituted with one or more substituents independently selected from 3- to 6-membered heterocycloalkyl groups optionally substituted with alkyl groups. In some embodiments, ring A is selected from C3-C6 saturated cycloalkyl groups and 3- to 6-membered saturated heterocycloalkyl groups, each of which is a halogen, -C(O)OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl and 1-4 C 1-6 It is optionally substituted with 1 to 4 substituents independently selected from 3 to 6-membered heterocycloalkyl groups that are optionally substituted with alkyl groups.

[0379] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7) ), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC-7), (VID- For compounds of type 1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), ring A is selected from cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is a halogen, -C(O)OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl and one or more C 1-6 Ring A is optionally substituted with one or more substituents independently selected from 3- to 6-membered heterocycloalkyl groups optionally substituted with alkyl groups; however, if ring B is pyrazolyl, then ring A is not N-Boc pyrrolidinyl. In some embodiments, ring A is selected from cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is halogen, -C(O)OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl and one or more C 1-6 Optionally substituted with one or more substituents independently selected from 3- to 6-membered heterocycloalkyl groups optionally substituted with alkyl groups; however, if ring B is pyrazolyl, then ring A is not N-Boc pyrrolidinyl; R 11 Independently, hydrogen and C exist in each of their respective forms. 1-4 Selected from alkyl groups.

[0380] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7) ), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC-7), (VID- For compounds of type 1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), ring A is selected from cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is a halogen, -C(O)OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl and one or more C 1-6 The ring A is optionally substituted with one or more substituents independently selected from 3- to 6-membered heterocycloalkyl groups optionally substituted with alkyl groups. In some embodiments, ring A is selected from cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is a halogen, -C(O)OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl and 1-4 C 1-6 Optionally substituted with 1 to 4 substituents independently selected from 3 to 6-membered heterocycloalkyl groups optionally substituted with alkyl groups; however, if ring B is pyrazolyl, ring A is not N-Boc pyrrolidinyl.

[0381] In some embodiments, formulas (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA- 7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC-7), (VI For compounds D-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), ring A is selected from cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is -F, -CH3, [ka] Optionally substituted with one or more substituents independently selected from; however, if ring B is pyrazolyl, then ring A is not N-Boc pyrrolidiny...

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