LYSINE ACETYLTRANSFERASE 6A (KAT6A) INHIBITORS AND USES THEREOF - Patent application

Abstract

Described herein are KAT6A inhibitors and pharmaceutical compositions comprising said KAT6A inhibitors. The subject compounds and compositions are useful for treating diseases or disorders associated with KAT6A.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This patent application claims the benefit of International Application No. PCT / CN2021 / 130956, filed November 16, 2021, International Application No. PCT / CN2022 / 079709, filed March 8, 2022, and International Application No. PCT / CN2022 / 126722, filed October 21, 2022, each of which is incorporated by reference in its entirety herein. [Background technology]

[0002] Lysine acetyltransferase 6A (KAT6A) belongs to the MYST family of acetyltransferases and was first discovered approximately 25 years ago. KAT6A controls fundamental cellular processes including gene transcription, cellular senescence, cardiac septum development, memory T cell diversity, and maintenance of normal hematopoietic stem cells. Dysregulation of KAT6A acetyltransferase activity or aberrant expression of KAT6A has been linked to oncogenic functions in many cancers, including leukemia, glioma, endometrial serous carcinoma, and breast cancer. Thus, compounds that inhibit KAT6A are potential agents for treating various cancers. Summary of the Invention

[0003] In one embodiment, the compound of formula (I)

[0004] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 1 is CR 1a or N, Y 2 is CR 2a or N, Y 3 is CR 3a or N, Y 4 is CR 4aor N, Y 5 is CR 5a or N, Z 1 is CR 1b or N, Z 2 is CR 2b or N, Z 3 is CR 3b or N and Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 At least one of is N, X is -C(R 6 )(R 6a )-, -O-, and -N(R 7 )- is selected from R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a and each R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O)2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13, -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0005] In some embodiments, the compound of formula (I')

[0006] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 1 is CR 1a or N, Y 2 is CR 2a or N, Y 3 is CR 3a or N, Y 4 is CR 4a or N, Y 5 is CR5a or N, Z 1 is CR 1b or N, Z 2 is CR 2b or N, Z 3 is CR 3b or N, X is -O- or -S-; or X is -C(R 6 )(R 6a )- and -N(R 7 )-, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 At least one of is N, R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a and each R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13, -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 Optionally substituted with 1, 2, or 3 groups independently selected from C(O)R.

[0007] In some embodiments, the compound of formula (I')

[0008] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 1 is CR 1a or N, Y 2 is CR 2a or N, Y 3 is CR 3a or N, Y 4 is CR 4a or N, Y 5 is CR 5a or N, Z 1 is CR 1b or N, Z2 is CR 2b or N, Z 3 is CR 3b or N, X is -O-, R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O)2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a and each R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11)-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0009] In some embodiments, the compound of formula (I) or formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, has the formula (Ia):

[0010] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0011] In some embodiments, provided herein is a compound of Formula (I), (I′), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1a and R 5a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments, provided herein is a compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1a and R 5a are independently hydrogen and -OR 10 In some embodiments, provided herein is a compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1a and R 5a-OR 10 In some embodiments, provided herein is a compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 10 is C 1-6 In some embodiments, provided herein are compounds of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 10 Ha-CH 3 In some embodiments, provided herein is a compound of formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a In some embodiments, provided herein is a compound of formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 2 is CR 2a and Y 3 is N, and Y 4 is CR 4a In some embodiments, provided herein is a compound of formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 2 is N and Y 3 is CR 3a and Y 4 is N. In some embodiments, provided herein is a compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a In some embodiments, provided herein is a compound of formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z 1 is CR 1b and Z2 is CR 2b and Z 3 is CR 3b In some embodiments, provided herein is a compound of formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z 1 is N and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments, provided herein is a compound of formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z 1 is CR 1b and Z 2 is N, and Z 3 is CR 3b In some embodiments, provided herein is a compound of formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is N. In some embodiments, provided herein is a compound of Formula (I), (I′), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments, provided herein is a compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, and C 1-6In some embodiments, provided herein is a compound of Formula (I), (I′), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b is hydrogen.

[0012] In another embodiment, the compound of formula (II)

[0013] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein X is -C(R 6 )(R 6a )-, -O-, and -N(R 7 )- is selected from R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 7 is hydrogen, C 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 8a , R 8b , R 8c , R 8d , R 8e , R 9b , and R 9c are each independently hydrogen, halogen, or C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 9a is C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C6-10 Aryl, C 1-9 Heteroaryl, -OR 14 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl and C 3-6 Cycloalkyl is R 15c and is substituted with one, two, or three groups selected from 2-6 Alkenyl, C 2-6 Alkynyl, C2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15d or R 9a and R 9b are combined to form C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 2-9 Forming a heteroaryl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, and C 2-9 Heteroaryl is R 15e and optionally substituted with one, two, or three groups selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 14 are independently hydrogen, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 2-6 Alkenyl, C 2-6 Alkynyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a , each R 15b , each R 15c , each R 15d , each R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12)C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0014] In some embodiments, provided herein is a compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9b is hydrogen, halogens, and C 1-6 In some embodiments, provided herein is a compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9b In some embodiments, provided herein is a compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a -OR 14In some embodiments, provided herein is a compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 14 is C 1-6 In some embodiments, provided herein is a compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a and R 9b are combined to form C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 2-9 Forming a heteroaryl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, and C 2-9 Heteroaryl is R 15e In some embodiments, provided herein is a compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a and R 9b are combined to form R 15e C optionally substituted with one, two, or three groups selected from 2-9 In some embodiments, provided herein is a compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a and R 9b are combined to form halogens, C 1-6 Alkyl, and C 1-6 C optionally substituted with one, two, or three groups selected from haloalkyl 2-9 Forms a heterocycloalkyl.

[0015] In some embodiments, provided herein is a compound of Formula (I), (I′), (Ia), or (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is —C(R 6 )(R 6aIn some embodiments, provided herein is a compound of Formula (I), (I′), (Ia), or (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 and R 6a are independently hydrogen, halogen, C 1-6 In some embodiments, provided herein is a compound of Formula (I), (I'), (Ia), or (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein R is selected from alkyl, -alkyl, and -OH. 6 and R 6a is hydrogen. In some embodiments, provided herein is a compound of Formula (I), (I'), (Ia), or (II), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is -O-.

[0016] In another embodiment, the compound of formula (III)

[0017] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein X is -O- and -N(R 7 )- is selected from R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 8a , R 8b , R 8c , R 8d , R 8e , R 9b , and R 9c are each independently hydrogen, halogen, or C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 9a is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -OR 14 is selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 14 is C1-6 Alkyl and C 3-6 cycloalkyl, and each R 15a and each R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10)(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0018] In some embodiments, provided herein is a compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9b is hydrogen, halogens, and C 1-6 In some embodiments, provided herein is a compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R is selected from alkyl. 9b In some embodiments, provided herein is a compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a -OR 14 In some embodiments, provided herein is a compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 14 is C 1-6 In some embodiments, provided herein is a compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a HA-OCH 3It is.

[0019] In some embodiments, provided herein is a compound of Formula (III), or a pharma- ceutically acceptable salt, or solvate thereof, wherein X is --O--.

[0020] In some embodiments, provided herein is a compound of Formula (II) or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 8a and R 8e are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments, provided herein is a compound of formula (II) or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 8a and R 8e are independently hydrogen and -OR 10 In some embodiments, provided herein is a compound of formula (II) or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 8a and R 8e -OR 10 In some embodiments, provided herein is a compound of formula (II) or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 10 is C 1-6 In some embodiments, provided herein are compounds of formula (II) or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 10 Ha-CH 3 In some embodiments, provided herein is a compound of formula (II) or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 8b , R 8c , R 8d , and R 9c are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10In some embodiments, provided herein is a compound of formula (II) or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 8b , R 8c , R 8d , and R 9c are independently hydrogen, halogen, and C 1-6 In some embodiments, provided herein is a compound of formula (II) or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 8b , R 8c , R 8d , and R 9c is hydrogen.

[0021] In some embodiments, formula (IV)

[0022] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15c and optionally substituted with one, two, three, or four groups selected from Z 1 is CR 1b or N, Z 2 is CR 2b or N, Z 3 is CR 3b or N, R 1 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15aand optionally substituted with one, two, or three groups selected from R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O)2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from Or, R 2b and R 3b Together, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Forming a heteroaryl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15e and optionally substituted with one, two, three, or four groups selected from Each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10)(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on adjacent carbons 15e Together, C 2 Forming an alkenylene, Alternatively, two R on the same atom 15e Together, C 3-6 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12)S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on different atoms 15e Together, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, or C 1-6 is haloalkyl, R 12 are each independently hydrogen, C 1-6 Alkyl, or C 1-6 haloalkyl, and R 13 are each independently hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 It is optionally substituted with one, two, or three groups selected from heteroaryl.

[0023] In some embodiments, formula (V)

[0024] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is R 15c C optionally substituted with one, two, three, or four groups selected from 1-9 is heteroaryl, Z 1 is CR 1b or N, R 1 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15a and optionally substituted with one, two, or three groups selected from R 1b is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from X is -C(R 6 )(R 6a )-, -S-, -O-, or -N(R 7 )-and R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; Or, R 6 and R 6a come together to form oxo, R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; Ring A is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 is heteroaryl, Each R 15a , each R 15b , and each R 15care independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on adjacent carbons 15e Together, C 2 Forming an alkenylene, Alternatively, two R on the same atom 15e Together, C 3-6 Cycloalkyl or C 2-9heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on different atoms 15eTogether, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R11 Optionally substituted with 1, 2, or 3 groups independently selected from n is 0 to 6; R 10 are hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are hydrogen, C 1-6 Alkyl, or C 1-6 is haloalkyl, R 12 are hydrogen, C 1-6 Alkyl, or C 1-6 haloalkyl, and R 13 are hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 It is optionally substituted with one, two, or three groups selected from heteroaryl.

[0025] In some embodiments, formula (VI)

[0026] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15c and optionally substituted with one, two, three, or four groups selected from Z 1 is CR 1b or N, R 1 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15a and optionally substituted with one, two, or three groups selected from R 1b is hydrogen, halogen, C 1-6 Alkyl, C 1-6Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from X is -C(R 6 )(R 6a )-, -S-, -O-, or -N(R 7 )-and R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11)-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; Or, R 6 and R 6a come together to form oxo, R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; Ring B is C 3-6 Cycloalkyl, C 6-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 is heteroaryl, Each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O)2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on adjacent carbons 15e Together, C 2 Forming an alkenylene, Alternatively, two R on the same atom 15e Together, C 3-6 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13, -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on different atoms 15e Together, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10)(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from n is 0 to 6; R 10 are hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are hydrogen, C 1-6 Alkyl, or C 1-6 is haloalkyl, R 12 are hydrogen, C 1-6 Alkyl, or C 1-6 haloalkyl, and R 13 are hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 It is optionally substituted with one, two, or three groups selected from heteroaryl.

[0027] In some embodiments, provided herein is a compound of Formula (I), (I′), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments, provided herein is a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 In some embodiments, provided herein is a compound of Formula (I), (I'), (Ia), (II), or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted. 1 In some embodiments, provided herein is a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is unsubstituted pyridinyl.

[0028] In some embodiments, provided herein is a compound of Formula (I), (I′), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15aIn some embodiments, provided herein is a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 In some embodiments, provided herein is a compound of Formula (I), (I'), (Ia), (II), or (III), or a pharma- ceutically acceptable salt or solvate thereof, wherein R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted. 1 In some embodiments, provided herein is a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is unsubstituted pyridinyl.

[0029] In one aspect, disclosed herein are compounds of Table 1A, Table 1B, and Table 1C, or pharma- ceutically acceptable salts or solvates thereof. In one aspect, disclosed herein are pharmaceutical compositions comprising compounds of Table 1A, Table 1B, and Table 1C, or pharma- ceutically acceptable salts or solvates thereof, and at least one pharma- ceutically acceptable excipient.

[0030] In another aspect, disclosed herein is a pharmaceutical composition comprising a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, and at least one pharma- ceutically acceptable excipient.

[0031] In another aspect, there is a method of treating cancer in a mammal, the method comprising administering to the mammal a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof.

[0032] In some embodiments, there is a method of treating cancer in a mammal in need of such treatment, the method comprising administering to the mammal a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, wherein the cancer is selected from the group consisting of lung cancer, mesothelioma, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, gastric cancer, hepatocellular carcinoma, colon cancer, breast cancer, uterine cancer, or ovarian cancer. The cancer is selected from endometrial cancer, cervical cancer, vaginal cancer, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal gland cancer, soft tissue sarcoma, cancer of the urethra, cancer of the penis, prostate cancer, hematological malignancies, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvis cancer, central nervous system (CNS) neoplasms, primary CNS lymphoma, spinal axis tumors, glioblastoma, brain stem glioma, pituitary adenoma, or a combination of two or more of the foregoing cancers.

[0033] In some embodiments, there is a method of treating cancer in a mammal in need thereof, comprising administering a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, to the mammal, wherein the cancer is selected from ER-positive breast cancer, glioblastoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), melanoma, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer (CRC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), leukemia, lymphoma or multiple myeloma, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and non-Hodgkin's lymphoma.

[0034] In some embodiments, there is a method of treating cancer in a mammal in need of treatment, the method comprising administering to the mammal a compound of Formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or a pharma- ceutically acceptable salt or solvate thereof, wherein the cancer is a solid tumor having KAT6A / 6B amplification or overexpression, or a leukemia or solid tumor having a KAT6A / 6B fusion protein resulting from a chromosomal translocation.

[0035] INCORPORATION BY REFERENCE All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] definition In the following description, specific details are set forth to provide a thorough understanding of various embodiments. However, it will be understood that those skilled in the art may practice the present disclosure without these details. In other instances, well-known structures have not been shown or described in detail so as not to unnecessarily obscure the description of the embodiments. Unless otherwise required by context, throughout the following specification and claims, the word "comprise" and variations thereof (e.g., "comprises" or "comprising") are intended to be interpreted in an open and inclusive sense, i.e., "including, but not limited to." Additionally, the headings provided herein are for convenience only and do not interpret the scope or meaning of the subject invention.

[0037] References throughout this specification to "some embodiments" or "embodiments" mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment. Thus, the appearances of the phrases ("in one embodiment") or ("in an embodiment") throughout this specification are not necessarily all referring to the same embodiment. Moreover, particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Similarly, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. It should also be noted that the term "or" is generally used in its sense to include "and / or" unless the content clearly dictates otherwise.

[0038] As used herein, the following terms have the following meanings unless otherwise specified.

[0039] "Oxo" refers to =O.

[0040] "Carboxyl" refers to --COOH.

[0041] "Cyano" refers to -CN.

[0042] "Alkyl" refers to a straight or branched chain saturated hydrocarbon monoradical having from 1 to about 10 carbon atoms, more preferably from 1 to 6 carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl, and hexyl, as well as longer alkyl groups such as heptyl, octyl, and the like. Whenever it appears in this specification, "C 1 -C 6 Alkyl" or "C 1-6 Numeric ranges such as "alkyl" mean that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the definition also includes occurrences of the term "alkyl" where no numerical range is specified. In some embodiments, alkyl is C 1-10 In some embodiments, alkyl is C 1-6 In some embodiments, alkyl is C 1-5 In some embodiments, alkyl is C 1-4 In some embodiments, alkyl is C 1-3 Unless otherwise specified in the specification, an alkyl group can be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, an alkyl group is an oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH 2, or -NO 2 In some embodiments, the alkyl is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkyl is optionally substituted with halogen.

[0043] "Alkenyl" refers to a straight or branched chain hydrocarbon monoradical having one or more carbon-carbon double bonds and having from 2 to about 10 carbon atoms, more preferably from 2 to about 6 carbon atoms. The group may be in either the cis or trans conformation about the double bond and should be understood to include both isomers. Examples include, but are not limited to, ethenyl (-CH=CH 2 ), 1-propenyl (-CH 2 CH=CH 2 ), isopropenyl [-C(CH 3 )=CH 2 ], butenyl, 1,3-butadienyl, etc. Whenever appearing in this specification, "C 2 -C 6 alkenyl" or "C 2-6 Numerical ranges such as "alkenyl" mean that the alkenyl group can consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although this definition also includes the appearance of the term "alkenyl" where no numerical range is specified. Unless otherwise specified in the specification, an alkenyl group can be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, an alkenyl is an oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, the alkenyl is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkenyl is optionally substituted with halogen.

[0044] "Alkynyl" refers to an optionally substituted straight or branched chain hydrocarbon monoradical having one or more carbon-carbon triple bonds and having from 2 to about 10 carbon atoms, more preferably from 2 to about 6 carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl, and the like. Whenever it appears in this specification, "C 2 -C 6 alkynyl" or "C 2-6 Numerical ranges such as "alkynyl" mean that the alkynyl group can consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, but the definition also includes the appearance of the term "alkynyl" when no numerical range is specified. Unless otherwise specified in the specification, alkynyl groups can be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, alkynyl is oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, the alkynyl is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkynyl is optionally substituted with halogen.

[0045] "Alkylene" refers to a straight or branched divalent hydrocarbon chain. Unless otherwise specified in the specification, an alkylene group can be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, an alkylene is an oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH 2 , or -NO 2In some embodiments, the alkylene is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkylene is optionally substituted with halogen.

[0046] "Alkoxy" is a group of formula -OR a R refers to the radical of a is an alkyl radical as defined. Unless otherwise specified in the specification, an alkoxy group can be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, an alkoxy is a halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, an alkylene is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, an alkoxy is optionally substituted with halogen.

[0047] "Aryl" refers to a radical derived from a hydrocarbon ring system containing 6 to 30 carbon atoms and at least one aromatic ring. The aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems. In some embodiments, the aryl is a 6-membered aryl (phenyl). Aryl radicals include, but are not limited to, aryl radicals derived from anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene hydrocarbon ring systems. Unless otherwise specified in the specification, an aryl can be optionally substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, an aryl can be optionally substituted with halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, the aryl is optionally substituted with halogen.

[0048] "Cycloalkyl" refers to a partially or fully saturated monocyclic or polycyclic carbocycle, which may include fused (when fused with an aryl or heteroaryl ring, the cycloalkyl is attached through a non-aromatic ring atom), spiro, or bridged ring systems. In some embodiments, cycloalkyls are fully saturated. Representative cycloalkyls include, but are not limited to, cycloalkyls having 3 to 15 carbon atoms (C 3 -C 15 Fully saturated cycloalkyl or C 3 -C 15 cycloalkenyl), 3 to 10 carbon atoms (C 3 -C 10 Fully saturated cycloalkyl or C 3 -C 10 cycloalkenyl), 3 to 8 carbon atoms (C 3 -C 8 Fully saturated cycloalkyl or C 3 -C 8 Cycloalkenyl), 3 to 6 carbon atoms (C 3 -C 6 Fully saturated cycloalkyl or C 3 -C 6 Cycloalkenyl), 3 to 5 carbon atoms (C 3 -C 5 Fully saturated cycloalkyl or C 3 -C 5 cycloalkenyl), or 3-4 carbon atoms (C 3 -C 4 Fully saturated cycloalkyl or C 3 -C 4In some embodiments, the cycloalkyl is a 3- to 10-membered fully saturated cycloalkyl, or a 3- to 10-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 3- to 6-membered fully saturated cycloalkyl, or a 3- to 6-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 5- to 6-membered fully saturated cycloalkyl, or a 5- to 6-membered cycloalkenyl. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, and bicyclo[3.3.2]decane, as well as 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Partially saturated cycloalkyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless otherwise stated in the specification, cycloalkyl is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, cycloalkyl is optionally substituted with, for example, oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, cycloalkyl is optionally substituted with halogen.

[0049] "Halo" or "halogen" refers to bromo, chloro, fluoro, or iodo. In some embodiments, the halogen is fluoro or chloro. In some embodiments, the halogen is fluoro.

[0050] "Haloalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, such as trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like.

[0051] "Hydroxyalkyl" refers to an alkyl radical, as defined above, substituted with one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Hydroxyalkyl includes, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[0052] "Aminoalkyl" refers to an alkyl radical, as defined above, substituted with one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Aminoalkyl includes, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl.

[0053] "Heteroalkyl" refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from atoms other than carbon, e.g., oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or combinations thereof. The heteroalkyl is attached to the remainder of the molecule at a carbon atom of the heteroalkyl. In one embodiment, the heteroalkyl is C 1 -C 6 Heteroalkyl, where the heteroalkyl is composed of 1 to 6 carbon atoms and one or more atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or combinations thereof, where the heteroalkyl is attached to the remainder of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyls include, for example, -CH 2 OCH 3 , -CH 2 CH 2 OCH 3 , -CH 2 CH 2 OCH 2 CH 2 OCH 3 , -CH(CH 3 )OCH 3 , -CH 2 NHCH 3 , -CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 3 , or -CH 2 CH 2 N(CH 3 ) 2 Unless otherwise stated in the specification, heteroalkyl is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, heteroalkyl is oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2In some embodiments, heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, heteroalkyl is optionally substituted with halogen.

[0054] "Heterocycloalkyl" refers to a 3-24 membered partially or fully saturated ring radical containing 2-23 carbon atoms and 1-8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, silicon, and sulfur. In some embodiments, a heterocycloalkyl is fully saturated. In some embodiments, a heterocycloalkyl contains 1-3 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, a heterocycloalkyl contains 1-3 heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, a heterocycloalkyl contains 1-3 nitrogens. In some embodiments, a heterocycloalkyl contains 1 or 2 nitrogens. In some embodiments, a heterocycloalkyl contains 1 nitrogen. In some embodiments, a heterocycloalkyl contains 1 nitrogen and 1 oxygen. Unless otherwise specified in the specification, a heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with an aryl or heteroaryl ring, the heterocycloalkyl is attached through a non-aromatic ring atom), spiro, or bridged ring systems, and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical may be optionally oxidized and the nitrogen atom may be optionally quaternized. Representative heterocycloalkyls include, but are not limited to, heterocyclic rings having 2 to 15 carbon atoms (C 2 -C 15 Fully saturated heterocycloalkyl or C 2 -C 15 heterocycloalkenyl), 2 to 10 carbon atoms (C 2 -C 10 Fully saturated heterocycloalkyl or C 2 -C10 heterocycloalkenyl), 2 to 8 carbon atoms (C 2 -C 8 Fully saturated heterocycloalkyl or C 2 -C 8 heterocycloalkenyl), 2 to 7 carbon atoms (C 2 -C 7 Fully saturated heterocycloalkyl or C 2 -C 7 heterocycloalkenyl), 2 to 6 carbon atoms (C 2 -C 6 Fully saturated heterocycloalkyl or C 2 -C 7 heterocycloalkenyl), 2 to 5 carbon atoms (C 2 -C 5 Fully saturated heterocycloalkyl or C 2 -C 5 heterocycloalkenyl), or 2 to 4 carbon atoms (C 2 -C 4 Fully saturated heterocycloalkyl or C 2 -C 4Examples of such heterocycloalkyl radicals include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperaz ... Examples of heterocycloalkyl include lydonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl, and 2-oxo-1,3-dioxol-4-yl. The term "heterocycloalkyl" also includes all cyclic forms of carbohydrates, including, but not limited to, monosaccharides, disaccharides, and oligosaccharides. In some embodiments, heterocycloalkyls have 2 to 10 carbons in the ring. It is noted that when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including heteroatoms) that make up the heterocycloalkyl (i.e., the skeletal atoms of the heterocycloalkyl ring). In some embodiments, the heterocycloalkyl is a 3-8 membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3-7 membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3-6 membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 4-6 membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5-6 membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3-8 membered heterocycloalkenyl.In some embodiments, the heterocycloalkyl is a 3-7 membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3-6 membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 4-6 membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 5-6 membered heterocycloalkenyl. Unless otherwise specified herein, the heterocycloalkyl can be optionally substituted as described below, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the heterocycloalkyl is an oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF. 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, heterocycloalkyl is optionally substituted with halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, heterocycloalkyl is optionally substituted with halogen.

[0055] "Heteroaryl" refers to a 5-14 membered ring system radical containing 1-13 carbon atoms, 1-6 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur, and at least one aromatic ring. In some embodiments, the heteroaryl contains 1-3 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl contains 1-3 heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heteroaryl contains 1-3 nitrogens. In some embodiments, the heteroaryl contains 1 or 2 nitrogens. In some embodiments, the heteroaryl contains 1 nitrogen. The heteroaryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is joined by an aromatic ring atom) or bridged ring systems, and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may be optionally oxidized, and the nitrogen atom may be optionally quaternized. In some embodiments, the heteroaryl is a 5-10 membered heteroaryl. In some embodiments, the heteroaryl is a 5-6 membered heteroaryl. In some embodiments, the heteroaryl is a 6 membered heteroaryl. In some embodiments, the heteroaryl is a 5 membered heteroaryl.Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, Includes isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless otherwise specified in the specification, a heteroaryl can be optionally substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, a heteroaryl can be optionally substituted with halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF. 3 , -OH, -OMe, -NH 2 , or -NO 2In some embodiments, heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, the heteroaryl is optionally substituted with halogen.

[0056] The term "optionally" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances in which the event or circumstance occurs and instances in which it does not occur. For example, "optionally substituted alkyl" means "alkyl" or "substituted alkyl" as defined above. Additionally, an optionally substituted group can be unsubstituted (e.g., -CH 2 CH 3 ) or completely substituted (e.g., -CF 2 CF 3 ) or monosubstituted (e.g., -CH 2 CH 2 F) or substituted at levels ranging between fully substituted and monosubstituted (e.g., -CH 2 CHF 2 , -CH 2 CF 3 , -CF 2 CH 3 , -CFHCHF 2 etc.) With respect to any group that contains one or more substituents, one of skill in the art will understand that such groups are not intended to introduce any substitutions or substitution patterns that are sterically impractical and / or synthetically unfeasible. Thus, any described substituents should generally be understood as having a maximum molecular weight of about 1,000 daltons, and more specifically, up to about 500 daltons.

[0057] "Effective amount" or "therapeutically effective amount" refers to the amount of a compound administered to a mammalian subject, either in a single dose or as part of a series, that is effective to produce the desired therapeutic effect.

[0058] "Treatment" of an individual (e.g., a mammal such as a human) or cell is any type of intervention used in an attempt to alter the natural course of the individual or cell. In some embodiments, treatment involves administration of a pharmaceutical composition after the initiation of a pathological event or contact with a pathogen, and involves stabilization of disease (e.g., the disease does not worsen) or amelioration of disease.

[0059] compound Described herein are compounds of formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or pharma- ceutically acceptable salts or solvates thereof, which are KAT6A inhibitors and are useful for treating diseases or disorders associated with KAT6A inhibition. In some embodiments, compounds of formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or pharma-ceutically acceptable salts or solvates thereof, are useful for treating cancer.

[0060] In some embodiments, formula (I)

[0061] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 1 is CR 1a or N, Y 2 is CR 2a or N, Y 3 is CR 3a or N, Y 4 is CR 4a or N, Y 5 is CR 5a or N, Z 1 is CR 1b or N, Z 2 is CR 2b or N, Z3 is CR 3b or N and Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 At least one of is N, X is -C(R 6 )(R 6a )-, -O-, and -N(R 7 )- is selected from R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13, -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a and each R 15b are each independently halogen, oxo, -CN, C1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O)2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0062] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is N.

[0063] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N.

[0064] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 3 is CR 3a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 3 is N.

[0065] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 4 is CR 4a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 4 is N.

[0066] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 5 is CR 5a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 5 is N.

[0067] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a It is.

[0068] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y is selected from 1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a are independently hydrogen and -OR 10 In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y is selected from 1 is CR1a and Y 5 is CR 5a and R 1a and R 5a -OR 10 In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a -OR 10 and R 10 is C 1-6 In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y is alkyl. 1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a -OR 10 and R 10 Ha-CH 3 It is.

[0069] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is N.

[0070] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 2 is CR 2b In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 2 is N.

[0071] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 3 is CR 3bIn some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 3 is N.

[0072] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a and Y 5 is CR 5a and Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a and Y 5 is CR 5a and Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 Of these, Y 2 is N. In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 , Y2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 and Y is N. In some embodiments, Y 2 If N, then R 1a and R 5a -OR 10 In some embodiments, Y 2 If N, then R 1a and R 5a are independent, -OC 1-6 Alkyl and -OC 1-6 In some embodiments, Y is selected from haloalkyl. 2 If N, then R 1a and R 5a HA-OCH 3 It is.

[0073] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a and Y 3 is N, and Y 4 is CR 4a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N and Y 3 is CR 3a and Y 4 is N. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR4a It is.

[0074] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and Y 2 is CR 2a and Y 3 is N, and Y 4 is CR 4a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and Y 2 is N and Y 3 is CR 3a and Y 4 is N. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a It is.

[0075] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1band Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is N and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2 is N, and Z 3 is CR 3b In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is N.

[0076] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, and C 1-6 In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R3a , R 4a , R 1b , R 2b , and R 3b In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1b and R 2b is hydrogen, and R 3b -OR 10 and R 10 is C 1-6 In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1b and R 2b is hydrogen, and R 3b -OR 10 and R 10 is C substituted with one, two or three halogens 1-6 It is an alkyl.

[0077] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 1a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 1a is hydrogen. In some embodiments, R 1a is C 1-6 In some embodiments, R 1a is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 1a is C 1-6 In some embodiments, R 1a -OCF 3It is.

[0078] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 2a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 2a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 2a is hydrogen. In some embodiments, R 2a is C 1-6 In some embodiments, R 2a is C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0079] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 3a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl is R 15b In some embodiments, R 3a is hydrogen, halogen, C 1-6 Alkyl, C 1-6Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl is optionally substituted. In some embodiments, R 3a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkynyl, or C 2-6 In some embodiments, R 3a is hydrogen. In some embodiments, R 3a is C 1-6 In some embodiments, R 3a is C 1-6 In some embodiments, R 3a is C 1-6 In some embodiments, R 3a is C 2-6 In some embodiments, R 3a is C 2-6 It is alkynyl.

[0080] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 4a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 4a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 4a is hydrogen. In some embodiments, R 4a is C 1-6 In some embodiments, R 4ais C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0081] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 5a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 5a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 5a is hydrogen. In some embodiments, R 5a is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 5a is C 1-6 In some embodiments, R 5a is C 1-3 In some embodiments, R 5a HA-OCH 3 It is.

[0082] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1b is hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 1b is hydrogen. In some embodiments, R 1b is halogen. In some embodiments, R 1b is C 1-6In some embodiments, R 1b is C 1-6 It is haloalkyl.

[0083] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 2b is hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 2b is hydrogen. In some embodiments, R 2b is halogen. In some embodiments, R 1b is C 1-6 In some embodiments, R 1b is C 1-6 It is haloalkyl.

[0084] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 3b is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 3b is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b is hydrogen. In some embodiments, R 3b is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b is C 1-6 In some embodiments, R 3b is C 1-3In some embodiments, R 3b is C 1-3 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b HA-OCH 3 In some embodiments, R 3b HA-OCH 2 F. In some embodiments, R 3b -OCF 3 In some embodiments, R 3b Ha-OCHF 2 In some embodiments, R 3b HA-OCH 2 CF 3 It is.

[0085] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a )- and R 6 and R 6a are independently hydrogen, halogen, C 1-6 In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, X is selected from -C(R 6 )(R 6a )- and R 6 and R 6a is hydrogen.

[0086] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, X is --O--.

[0087] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 is C 1-6 It is an alkyl.

[0088] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is optionally replaced by C 1-9 In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5- or 6-membered heteroaryl. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5-membered heteroaryl. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 6-membered heteroaryl. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is monocyclic heteroaryl. In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is a bicyclic heteroaryl. In some embodiments, R 1 is R 15a In some embodiments, R 1 is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R is optionally substituted with one, two, or three groups selected from alkoxyl. 1is oxo, -CN, amino, OH, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyl, and C 3-6 Optionally substituted with one, two, or three groups selected from cycloalkyl.

[0089] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6Haloalkyl, and -OR 10 In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0090] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a and R 15a is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0091] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted. 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted. 1 is unsubstituted pyrazolyl. In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1is unsubstituted imidazolyl. In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl. In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridinyl. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted thiazolyl. In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.

[0092] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0093] [ka] In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0094] [ka] each of which is selected from 1, 2, or 3 R 15a In some embodiments, R 1 teeth

[0095] [ka] In some embodiments, R 1 teeth

[0096] [ka] In some embodiments, R 1 teeth

[0097] [ka] In some embodiments, R 1 teeth

[0098] [ka] In some embodiments, R 1 teeth

[0099] [ka] In some embodiments, R 1 teeth

[0100] [ka] In some embodiments, R 1 teeth

[0101] [ka] In some embodiments, R 1 teeth

[0102] [ka] It is.

[0103] In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof,

[0104] [ka] teeth,

[0105] [ka] is selected from.

[0106] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl and C 3-6 The cycloalkyl is optionally substituted with one, two, or three groups selected from halogen and hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, or C 1-6 In some embodiments, R 10 is C 1-6 Alkyl or C 1-6 In some embodiments, R 10 is hydrogen. In some embodiments, R 10 Ha-CH 3 In some embodiments, R 10 Ha-CH 2 F. In some embodiments, R 10 -CHF 2 In some embodiments, R 10 Ha-CH 2 CF 3 In some embodiments, R 10 -CF 3 It is.

[0107] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 11 is hydrogen. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is C 1-6 It is an alkyl.

[0108] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 12 is hydrogen. In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is C 1-6 It is an alkyl.

[0109] In some embodiments of the compounds of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 In some embodiments of the compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 Alkyl or C 1-6 It is haloalkyl.

[0110] In some embodiments of the compound of Formula (I), or a pharma- ceutically acceptable salt or solvate thereof, each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0111] In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c is independent, C 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of Formula (I), each R 15a , each R 15b , and each R 15c are independent, -OR 10 It is.

[0112] In some embodiments, the compound of formula (Ia)

[0113] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 2 is CR 2a or N, Y 3 is CR 3a or N, Y 4 is CR 4a or N, Z 1 is CR 1b or N, Z 2 is CR 2b or N, Z 3 is CR 3b or N and Y 2 , Y 3 , Y 4 , Z 1 , Z 2 , and Z 3 At least one of is N, X is -C(R 6 )(R 6a )-, -O-, and -N(R 7 )- is selected from R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R15b and optionally substituted with one, two, or three groups selected from R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a and each R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13, -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10, -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0114] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1a and R 5a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1a and R 5a are independently hydrogen and -OR 10 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1a and R 5a -OR 10 In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1a and R 5a -OR 10 and R 10 is C 1-6 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1a and R 5a -OR 10 and R 10 Ha-CH 3 It is.

[0115] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a and Y 3 is N, and Y 4 is CR 4a In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N and Y 3 is CR 3a and Y 4 is N. In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a It is.

[0116] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N.

[0117] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 3 is CR 3a In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 3 is N.

[0118] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 4 is CR 4a In some embodiments of the compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, Y 4 is N.

[0119] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a and Y 3 is N, and Y 4 is CR 4aIn some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N and Y 3 is CR 3a and Y 4 is N. In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a It is.

[0120] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is N and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2 is N, and Z 3 is CR 3b In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is N.

[0121] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR1b In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is N.

[0122] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 2 is CR 2b In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 2 is N.

[0123] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 3 is CR 3b In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 3 is N.

[0124] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a and Y 5 is CR 5a and Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a and Y5 is CR 5a and Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 Of these, Y 2 is N. In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 and Y is N. In some embodiments, Y 2 If N, then R 1a and R 5a -OR 10 In some embodiments, Y 2 If N, then R 1a and R 5a are independent, -OC 1-6 Alkyl and -OC 1-6 In some embodiments, Y is selected from haloalkyl. 2 If N, then R 1a and R 5a HA-OCH 3 It is.

[0125] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R 3a , R 4a , R 1b , R 2b , and R 3bare independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, and C 1-6 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1b and R 2b is hydrogen, and R 3b -OR 10 and R 10 is C 1-6 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1b and R 2b is hydrogen, and R 3b -OR 10 and R 10 is C substituted with one, two or three halogens 1-6 It is an alkyl.

[0126] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 1a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 1a is hydrogen. In some embodiments, R 1a is C 1-6 In some embodiments, R 1a is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 1a is C 1-6 In some embodiments, R 1a -OCF 3 It is.

[0127] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 2a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 2a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 2a is hydrogen. In some embodiments, R 2a is C 1-6 In some embodiments, R 2a is C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0128] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 3a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl is R 15b In some embodiments, R 3a are hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl is optionally substituted. In some embodiments, R 3a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkynyl, or C 2-6 In some embodiments, R 3a is hydrogen. In some embodiments, R 3a is C 1-6 In some embodiments, R 3a is C 1-6 In some embodiments, R 3a is C 1-6 In some embodiments, R 3a is C 2-6 In some embodiments, R 3a is C 2-6 It is alkynyl.

[0129] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 4a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 4a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 4a is hydrogen. In some embodiments, R 4a is C 1-6 In some embodiments, R 4a is C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0130] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 5a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 5a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 5a is hydrogen. In some embodiments, R 5a is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 5a is C 1-6 In some embodiments, R 5a is C 1-3 In some embodiments, R5a HA-OCH 3 It is.

[0131] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1b is hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 1b is hydrogen. In some embodiments, R 1b is halogen. In some embodiments, R 1b is C 1-6 In some embodiments, R 1b is C 1-6 It is haloalkyl.

[0132] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 2b is hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 2b is hydrogen. In some embodiments, R 2b is halogen. In some embodiments, R 1b is C 1-6 In some embodiments, R 1b is C 1-6 It is haloalkyl.

[0133] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 3b is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10In some embodiments, R 3b is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b is hydrogen. In some embodiments, R 3b is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b is C 1-6 In some embodiments, R 3b is C 1-3 In some embodiments, R 3b is C 1-3 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b HA-OCH 3 In some embodiments, R 3b HA-OCH 2 F. In some embodiments, R 3b -OCF 3 In some embodiments, R 3b Ha-OCHF 2 In some embodiments, R 3b HA-OCH 2 CF 3 It is.

[0134] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a )- and R 6 and R 6a are independently hydrogen, halogen, C 1-6In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, X is selected from -C(R 6 )(R 6a )- and R 6 and R 6a is hydrogen.

[0135] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt, or solvate thereof, X is --O--.

[0136] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 In some embodiments of the compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 is C 1-6 It is an alkyl.

[0137] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is optionally replaced by C 1-9 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5- or 6-membered heteroaryl. In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5-membered heteroaryl. In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1is an optionally substituted 6-membered heteroaryl. In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is monocyclic heteroaryl. In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is a bicyclic heteroaryl. In some embodiments, R 1 is R 15a In some embodiments, R 1 is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R is optionally substituted with one, two, or three groups selected from alkoxyl. 1 is oxo, -CN, amino, OH, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyl, and C 3-6 Optionally substituted with one, two, or three groups selected from cycloalkyl.

[0138] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0139] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R15a In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0140] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted. 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted. 1 is unsubstituted pyrazolyl. In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted imidazolyl. In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl. In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridinyl. In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted thiazolyl. In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.

[0141] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0142] [ka] is selected from.

[0143] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0144] [ka] It is.

[0145] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0146] [ka] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0147] [ka] each of which is selected from 1, 2, or 3 R 15a In some embodiments, R 1 teeth

[0148] [ka] In some embodiments, R 1 teeth

[0149] [ka] In some embodiments, R 1 teeth

[0150] [ka] In some embodiments, R 1 teeth

[0151] [ka] In some embodiments, R 1 teeth

[0152] [ka] In some embodiments, R 1 teeth

[0153] [ka] In some embodiments, R 1 teeth

[0154] [ka] In some embodiments, R 1 teeth

[0155] [ka] It is.

[0156] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof,

[0157] [ka] teeth,

[0158] [ka] is selected from.

[0159] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl and C 3-6 The cycloalkyl is optionally substituted with one, two, or three groups selected from halogen and hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, or C 1-6 In some embodiments, R 10 is C 1-6 Alkyl or C 1-6 In some embodiments, R 10 is hydrogen. In some embodiments, R 10 Ha-CH 3 In some embodiments, R 10 Ha-CH 2 F. In some embodiments, R 10 -CHF 2 In some embodiments, R 10 Ha-CH 2 CF 3 In some embodiments, R 10 -CF 3 It is.

[0160] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is hydrogen, C 1-6Alkyl, and C 1-6 In some embodiments, R 11 In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is C 1-6 It is an alkyl.

[0161] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 12 In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is C 1-6 It is an alkyl.

[0162] In some embodiments of the compounds of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 In some embodiments of the compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 Alkyl or C 1-6 It is haloalkyl.

[0163] In some embodiments of the compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0164] In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c is independent, C 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of Formula (Ia), each R 15a , each R 15b , and each R 15c are independent, -OR 10 It is.

[0165] In some embodiments, the compound of formula (I')

[0166] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 1 is CR 1a or N, Y 2 is CR 2a or N, Y 3 is CR 3a or N, Y 4 is CR 4a or N, Y 5 is CR 5a or N, Z 1 is CR 1b or N, Z 2 is CR 2b or N, Z 3 is CR 3b or N, X is -O- or -S-; or X is -C(R 6 )(R 6a )- and -N(R 7 )-, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 At least one of is N, R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12)C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a and each R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0167] In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -O-. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -S-. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -O- or -S-. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a )- and Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 At least one of is N. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 At least one of is N.

[0168] In some embodiments, the compound of formula (I')

[0169] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein Y 1 is CR 1a or N, Y 2 is CR 2a or N, Y 3 is CR 3a or N, Y 4 is CR 4aor N, Y 5 is CR 5a or N, Z 1 is CR 1b or N, Z 2 is CR 2b or N, Z 3 is CR 3b or N, X is -O-, R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13, -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a and each R15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0170] In some embodiments, the compound of formula (I') has the structure of formula (Ia):

[0171] In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -O-. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -S-. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )-.

[0172] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is N.

[0173] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N.

[0174] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 3 is CR 3a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 3 is N.

[0175] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 4 is CR 4a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 4 is N.

[0176] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 5 is CR 5a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 5 is N.

[0177] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a It is.

[0178] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y is selected from 1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a are independently hydrogen and -OR 10 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y is selected from 1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a -OR 10 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a -OR 10 and R 10 is C 1-6 In some embodiments of the compounds of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y is alkyl. 1 is CR 1a and Y 5 is CR 5a and R 1a and R 5a -OR 10 and R 10 Ha-CH 3 It is.

[0179] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a and Y 3 is N, and Y 4 is CR 4a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is N and Y 3 is CR 3a and Y 4 is N. In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a It is.

[0180] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and Y 2 is CR 2a and Y 3 is N, and Y 4 is CR4a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and Y 2 is N and Y 3 is CR 3a and Y 4 is N. In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 5 is CR 5a and Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a It is.

[0181] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is N and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2 is N, and Z 3 is CR 3b In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2is CR 2b and Z 3 is N.

[0182] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is N.

[0183] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 2 is CR 2b In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 2 is N.

[0184] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 3 is CR 3b In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Z 3 is N.

[0185] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 2 is CR 2a and Y 3 is CR 3a and Y 4 is CR 4a and Y 5 is CR 5a and Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3bIn some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 is CR 1a and Y 2 is N and Y 3 is CR 3a and Y 4 is CR 4a and Y 5 is CR 5a and Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 Of these, Y 2 is N. In some embodiments of the compounds of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 and Y is N. In some embodiments, Y 2 If N, then R 1a and R 5a -OR 10 In some embodiments, Y 2 If N, then R 1a and R 5a are independent, -OC 1-6 Alkyl and -OC 1-6 In some embodiments, Y is selected from haloalkyl. 2 If N, then R 1a and R 5a HA-OCH 3 It is.

[0186] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently hydrogen, halogen, and C 1-6 In some embodiments of the compounds of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1b and R 2b is hydrogen, and R 3b -OR 10 and R 10 is C 1-6 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1b and R 2b is hydrogen, and R 3b -OR 10 and R 10 is C substituted with one, two or three halogens 1-6 It is an alkyl.

[0187] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 1a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 1a is hydrogen. In some embodiments, R 1a is C 1-6 In some embodiments, R 1a is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 1a is C 1-6 In some embodiments, R 1a -OCF 3 It is.

[0188] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 2a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 2a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 2a is hydrogen. In some embodiments, R 2a is C 1-6 In some embodiments, R 2a is C 1-6and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0189] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 3a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl is R 15b In some embodiments, R 3a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl is optionally substituted. In some embodiments, R 3a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkynyl, or C 2-6 In some embodiments, R 3a is hydrogen. In some embodiments, R 3a is C 1-6 In some embodiments, R 3a is C 1-6In some embodiments, R 3a is C 1-6 In some embodiments, R 3a is C 2-6 In some embodiments, R 3a is C 2-6 It is alkynyl.

[0190] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 4a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 4a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 4a is hydrogen. In some embodiments, R 4a is C 1-6 In some embodiments, R 4a is C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0191] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 5a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 5a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 5ais hydrogen. In some embodiments, R 5a is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 5a is C 1-6 In some embodiments, R 5a is C 1-3 In some embodiments, R 5a HA-OCH 3 It is.

[0192] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1b are hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 1b is hydrogen. In some embodiments, R 1b is halogen. In some embodiments, R 1b is C 1-6 In some embodiments, R 1b is C 1-6 It is haloalkyl.

[0193] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 2b are hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 2b is hydrogen. In some embodiments, R 2b is halogen. In some embodiments, R 1b is C 1-6In some embodiments, R 1b is C 1-6 It is haloalkyl.

[0194] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 3b is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 3b is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b is hydrogen. In some embodiments, R 3b is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b is C 1-6 In some embodiments, R 3b is C 1-3 In some embodiments, R 3b is C 1-3 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 3b HA-OCH 3 In some embodiments, R 3b HA-OCH 2 F. In some embodiments, R 3b -OCF 3 In some embodiments, R 3b Ha-OCHF 2 In some embodiments, R 3b HA-OCH 2 CF 3 It is.

[0195] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a )- and R 6 and R 6a are independently hydrogen, halogen, C 1-6 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is selected from -C(R 6 )(R 6a )- and R 6 and R 6a is hydrogen.

[0196] In some embodiments of the compounds of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is --O--.

[0197] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 is C 1-6 It is an alkyl.

[0198] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is optionally replaced by C 1-9 In some embodiments of the compounds of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1is an optionally substituted 5- or 6-membered heteroaryl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5-membered heteroaryl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 6-membered heteroaryl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is monocyclic heteroaryl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is a bicyclic heteroaryl. In some embodiments, R 1 is R 15a In some embodiments, R 1 is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R is optionally substituted with one, two, or three groups selected from alkoxyl. 1 is oxo, -CN, amino, OH, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyl, and C 3-6 Optionally substituted with one, two, or three groups selected from cycloalkyl.

[0199] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15aIn some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0200] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR10 is selected from.

[0201] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrazolyl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted imidazolyl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridinyl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted thiazolyl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1is unsubstituted pyrimidinyl. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.

[0202] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0203] [ka] In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0204] [ka] each of which is selected from 1, 2, or 3 R 15a In some embodiments, R 1 teeth

[0205] [ka] In some embodiments, R 1 teeth

[0206] [ka] In some embodiments, R 1 teeth

[0207] [ka] In some embodiments, R 1 teeth

[0208] [ka] In some embodiments, R 1 teeth

[0209] [ka] In some embodiments, R 1 teeth

[0210] [ka] In some embodiments, R 1 teeth

[0211] [ka] In some embodiments, R 1 teeth

[0212] [ka] It is.

[0213] In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof,

[0214] [ka] teeth,

[0215] [ka] is selected from.

[0216] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 In some embodiments, R10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl and C 3-6 The cycloalkyl is optionally substituted with one, two, or three groups selected from halogen and hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, or C 1-6 In some embodiments, R 10 is C 1-6 Alkyl or C 1-6 In some embodiments, R 10 is hydrogen. In some embodiments, R 10 Ha-CH 3 In some embodiments, R 10 Ha-CH 2 F. In some embodiments, R 10 -CHF 2 In some embodiments, R 10 Ha-CH 2 CF 3 In some embodiments, R 10 -CF 3 It is.

[0217] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 11 is hydrogen. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is C 1-6 It is an alkyl.

[0218] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is hydrogen, C1-6 Alkyl, and C 1-6 In some embodiments, R 12 is hydrogen. In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is C 1-6 It is an alkyl.

[0219] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 In some embodiments of the compound of formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 Alkyl or C 1-6 It is haloalkyl.

[0220] In some embodiments of the compound of Formula (I'), or a pharma- ceutically acceptable salt or solvate thereof, each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10)(R 11 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0221] In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R15c are independently halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c is independent, C 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of Formula (I'), each R 15a , each R 15b , and each R 15c are independent, -OR 10 It is.

[0222] In some embodiments of the compound of Formula (I), (I′), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b And each R 1a and each R 5a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 Each R 2a , each R 3a , each R 4a , each R 1b , each R 2b , and each R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C1-6 Haloalkyl, and -OR 10 Selected from R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, or C 2-9 In some embodiments of the compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5- or 6-membered heteroaryl. In some embodiments of the compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5-membered heteroaryl. In some embodiments of the compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 are pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, and pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are R 15a In some embodiments of the compound of Formula (I), (I′), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0223] [ka] In some embodiments of the compound of Formula (I), (I'), or (Ia), or a pharma- ceutically acceptable salt or solvate thereof, R 10 is C 1-6 Alkyl or C 1-6 It is haloalkyl.

[0224] In some embodiments, the compound of formula (II)

[0225] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein X is -C(R 6 )(R 6a )-, -O-, and -N(R 7 )- is selected from R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O)2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 8a , R 8b , R 8c , R 8d , R 8e , R 9b , and R 9c are each independently hydrogen, halogen, or C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13, -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from R 9a is C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 14 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl and C 3-6 Cycloalkyl is R 15c and is substituted with one, two, or three groups selected from 2-6 Alkenyl, C 2-6 Alkynyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15d or R 9a and R 9b are combined to form C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 2-9 Forming a heteroaryl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, and C2-9 Heteroaryl is R 15e and optionally substituted with one, two, or three groups selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 14 are independently hydrogen, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 2-6 Alkenyl, C 2-6 Alkynyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; and Each R 15a , each R 15b , each R 15c , each R 15d , each R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0226] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e are independently hydrogen and -OR 10 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e -OR 10 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e -OR 10 and R 10 is C 1-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e -OR 10 and R 10 Ha-CH3 It is.

[0227] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 8a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8a is hydrogen. In some embodiments, R 8a is C 1-6 In some embodiments, R 8a is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8a is C 1-6 In some embodiments, R 8a -OCF 3 It is.

[0228] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8e is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 8e is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8e is hydrogen. In some embodiments, R 8e is C 1-6In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8e is C 1-6 In some embodiments, R 8e is C 1-3 In some embodiments, R 8e HA-OCH 3 It is.

[0229] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8b , R 8c , R 8d , and R 9c are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8b , R 8c , R 8d , and R 9c are independently hydrogen, halogen, and C 1-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8b , R 8c , R 8d , and R 9c is hydrogen.

[0230] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8b is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 8b is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8b is hydrogen. In some embodiments, R 8b is C 1-6 In some embodiments, R 8b is C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0231] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8c is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl is R 15b In some embodiments, R 8c is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl is optionally substituted. In some embodiments, R 8c is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6Alkynyl, or C 2-6 In some embodiments, R 8c is hydrogen. In some embodiments, R 8c is C 1-6 In some embodiments, R 8c is C 1-6 In some embodiments, R 8c is C 1-6 In some embodiments, R 8c is C 2-6 In some embodiments, R 8c is C 2-6 It is alkynyl.

[0232] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 8d is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 8d is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8d is hydrogen. In some embodiments, R 8d is C 1-6 In some embodiments, R 8d is C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0233] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9c are hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15bIn some embodiments, R 9c is hydrogen. In some embodiments, R 9c is halogen. In some embodiments, R 9c is C 1-6 In some embodiments, R 9c is C 1-6 It is haloalkyl.

[0234] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9b is hydrogen, halogens, and C 1-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9b is hydrogen. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9b is halogen. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9b is C 1-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9b Ha-CH 3 It is.

[0235] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9b is hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 9b is hydrogen. In some embodiments, R 9b is halogen. In some embodiments, R 9b is C 1-6In some embodiments, R 9b is C 1-6 It is haloalkyl.

[0236] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a -OR 14 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a -OR 14 and R 14 is C 1-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a -OR 14 and R 14 -CF 3 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a -OR 14 and R 14 -CHF 2 It is.

[0237] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a is R 15c C substituted with one, two, or three groups selected from 3-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a is R 15c C substituted with one, two, or three groups selected from 3-6 cycloalkyl, R 15c are each independently a halogen, C 1-6 Alkyl, C 1-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a is R 15cC substituted with one, two, or three groups selected from 3-6 cycloalkyl, R 15c are each halogens.

[0238] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a is C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 14 In some embodiments, R 9a is C 1-6 Alkyl, C 1-6 Haloalkyl, or -OC 1-6 In some embodiments, R 9a Ha-OC 1-6 In some embodiments, R 9a Ha-OC 1-6 In some embodiments, R 9a HA-OCH 2 It's F.

[0239] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a and R 9b are combined to form C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 2-9 Forming a heteroaryl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, and C 2-9 Heteroaryl is R 15e In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a and R 9b are combined to form R 15e C optionally substituted with one, two, or three groups selected from 2-9In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a and R 9b are combined to form halogens, C 1-6 Alkyl, and C 1-6 C optionally substituted with one, two, or three groups selected from haloalkyl 2-9 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl and C 3-6 The cycloalkyl is optionally substituted with one, two, or three groups selected from halogen and hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, or C 1-6 In some embodiments, R 10 is C 1-6 Alkyl or C 1-6 In some embodiments, R 10 is hydrogen. In some embodiments, R 10 Ha-CH 3 In some embodiments, R 10 Ha-CH 2 F. In some embodiments, R 10 -CHF 2 In some embodiments, R 10 Ha-CH 2 CF 3 In some embodiments, R 10 -CF 3 It is.

[0240] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 9a and R 9b are combined to form a 5- to 7-membered ring. In some embodiments, R 9a and R 9b are combined to form a 6-membered ring. In some embodiments, R 9a and R 9b are combined to form a cycloalkyl. In some embodiments, R 9a and R 9b are combined to form a heterocycloalkyl. In some embodiments, R 9a and R 9b are combined to form a ring containing 1 or 2 oxygens and 0-2 nitrogens. In some embodiments, R 9a and R 9b are combined to form a ring containing one oxygen.

[0241] In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof,

[0242] [ka] teeth,

[0243] [ka] In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof,

[0244] [ka] teeth,

[0245] [ka] It is.

[0246] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 11 is hydrogen. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is C 1-6 It is an alkyl.

[0247] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 12 is hydrogen. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is C 1-6 It is an alkyl.

[0248] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 Haloalkyl, C 1-6 Alkyl, or C 3-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 It is an alkyl.

[0249] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 14 is hydrogen, C 1-6 Haloalkyl, or C 3-6 In some embodiments, R 14 is hydrogen or C1-6 In some embodiments, R 14 is C 1-6 In some embodiments, R 14 is hydrogen. In some embodiments, R 14 Ha-CH 2 F. In some embodiments, R 14 Ha-CH 2 CF 3 In some embodiments, R 14 -CF 3 It is.

[0250] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0251] In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl, C 3-10Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c is independent, C 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of Formula (II), each R 15a , each R 15b , and each R 15c are independent, -OR 10 It is.

[0252] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, X is -C(R 6 )(R 6a )- and R 6 and R 6a are independently hydrogen, halogen, C 1-6 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, X is selected from -C(R 6 )(R 6a )- and R 6 and R 6a is hydrogen.

[0253] In some embodiments of the compounds of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, X is --O--.

[0254] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 is C 1-6 It is an alkyl.

[0255] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is optionally replaced by C 1-9 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5- or 6-membered heteroaryl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5-membered heteroaryl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 6-membered heteroaryl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is monocyclic heteroaryl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is a bicyclic heteroaryl. In some embodiments, R 1 is R 15a In some embodiments, R 1 is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R is optionally substituted with one, two, or three groups selected from alkoxyl. 1is oxo, -CN, amino, OH, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyl, and C 3-6 Optionally substituted with one, two, or three groups selected from cycloalkyl.

[0256] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6Haloalkyl, and -OR 10 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0257] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0258] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted. 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted. 1 is unsubstituted pyrazolyl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1is unsubstituted imidazolyl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridinyl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted thiazolyl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.

[0259] In some embodiments of the compound of Formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0260] [ka] In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0261] [ka] each of which is selected from 1, 2, or 3 R 15a In some embodiments, R 1 teeth

[0262] [ka] In some embodiments, R 1 teeth

[0263] [ka] In some embodiments, R 1 teeth

[0264] [ka] In some embodiments, R 1 teeth

[0265] [ka] In some embodiments, R 1 teeth

[0266] [ka] In some embodiments, R 1 teeth

[0267] [ka] In some embodiments, R 1 teeth

[0268] [ka] It is.

[0269] In some embodiments, the compound of formula (III)

[0270] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein X is -O- and -N(R7 )- is selected from R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 is heteroaryl, R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 8a , R 8b , R 8c , R 8d , R 8e , R 9b , and R 9c are each independently hydrogen, halogen, or C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15band optionally substituted with one, two, or three groups selected from R 9a is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -OR 14 is selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 14 is C 1-6 Alkyl and C 3-6 cycloalkyl, and Each R 15a and each R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0271] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e are independently hydrogen and -OR 10 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e -OR 10 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e -OR 10 and R 10 is C 1-6 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8a and R 8e -OR 10 and R 10 Ha-CH 3 It is.

[0272] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8a is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 8a is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8ais hydrogen. In some embodiments, R 8a is C 1-6 In some embodiments, R 8a is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8a is C 1-6 In some embodiments, R 8a -OCF 3 It is.

[0273] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8e is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 8e is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8e is hydrogen. In some embodiments, R 8e is C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8e is C 1-6 In some embodiments, R 8e is C 1-3 In some embodiments, R 8e HA-OCH 3 It is.

[0274] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8b , R 8c , R 8d , and R 9care independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8b , R 8c , R 8d , and R 9c are independently hydrogen, halogen, and C 1-6 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8b , R 8c , R 8d , and R 9c is hydrogen.

[0275] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8b is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 8b is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8b is hydrogen. In some embodiments, R 8b is C 1-6 In some embodiments, R 8b is C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0276] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8c is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl is R 15b In some embodiments, R 8c is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl is optionally substituted. In some embodiments, R 8c is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkynyl, or C 2-6 In some embodiments, R 8c is hydrogen. In some embodiments, R 8c is C 1-6 In some embodiments, R 8c is C 1-6 In some embodiments, R 8c is C 1-6 In some embodiments, R 8c is C 2-6 In some embodiments, R 8c is C 2-6 It is alkynyl.

[0277] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 8d is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, R 8d is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 1-6 In some embodiments, R is an alkoxyl, which is optionally substituted with one, two, or three halogens. 8d is hydrogen. In some embodiments, R 8d is C 1-6 In some embodiments, R 8d is C 1-6 and alkoxyl, which is optionally substituted with one, two, or three halogens.

[0278] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9c is hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 9c is hydrogen. In some embodiments, R 9c is halogen. In some embodiments, R 9c is C 1-6 In some embodiments, R 9c is C 1-6 It is haloalkyl.

[0279] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9b is hydrogen, halogens, and C 1-6In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9b In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9b In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9b is C 1-6 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9b Ha-CH 3 It is.

[0280] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9b is hydrogen, halogen, C 1-6 Alkyl, or C 1-6 haloalkyl, C 1-6 Alkyl is R 15b In some embodiments, R 9b is hydrogen. In some embodiments, R 9b is halogen. In some embodiments, R 9b is C 1-6 In some embodiments, R 9b is C 1-6 It is haloalkyl.

[0281] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9a -OR 14 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9a -OR 14 and R 14 is C 1-6In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9a -OR 14 and R 14 Ha-CH 3 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9a -OR 14 and R 14 is C 3-6 In some embodiments, R 9a HA-OCH 2 It's F.

[0282] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9a is C 1-6 Alkyl, C 3-6 Cycloalkyl, or -OR 14 In some embodiments, R 9a is C 1-6 Alkyl, C 1-6 Cycloalkyl, or C 1-6 In some embodiments, R 9a is C 1-6 In some embodiments, R 9a is C 1-3 It is alkoxyl.

[0283] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9a In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9a is C 1-6 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 9a is C 3-6In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, X is -O-.

[0284] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, X is -N(R 7 )- and R 7 is C 1-6 It is an alkyl.

[0285] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 Cycloalkyl, C 1-6 Alkyl and C 3-6 The cycloalkyl is optionally substituted with one, two, or three groups selected from halogen and hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 Alkyl, or C 1-6 In some embodiments, R 10 is C 1-6 Alkyl or C 1-6 In some embodiments, R 10 is hydrogen. In some embodiments, R 10 Ha-CH 3 In some embodiments, R10 Ha-CH 2 F. In some embodiments, R 10 -CHF 2 In some embodiments, R 10 Ha-CH 2 CF 3 In some embodiments, R 10 -CF 3 It is.

[0286] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 11 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 11 is C 1-6 It is an alkyl.

[0287] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 12 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 12 is C 1-6 It is an alkyl.

[0288] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 Haloalkyl, C 1-6 Alkyl, or C 3-6 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 13 is C 1-6 It is haloalkyl.

[0289] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 14 is C 1-6 Alkyl or C 3-6 In some embodiments, R 14 is C 1-6 In some embodiments, R 14 is C 3-6 In some embodiments, R 14 Ha-CH 3 It is.

[0290] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, each R 15a and each R 15b are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of Formula (III), each R 15aand each R 15b are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (III), each R 15a and each R 15b are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (III), each R 15a and each R 15b are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0291] In some embodiments of the compound of Formula (III), each R 15a and each R 15b are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of Formula (III), each R 15a and each R 15b are independently halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (III), each R 15a and each R 15b are independently halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of Formula (III), each R 15a and each R 15b is independent, C 1-6 Alkyl, C 3-10Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (III), each R 15a and each R 15b is independent, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of Formula (III), each R 15a and each R 15b is independent, C 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of Formula (III), each R 15a and each R 15b are independent, -OR 10 It is.

[0292] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is optionally replaced by C 1-9 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5- or 6-membered heteroaryl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5-membered heteroaryl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 6-membered heteroaryl. In some embodiments of the compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is monocyclic heteroaryl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is a bicyclic heteroaryl. In some embodiments, R 1 is R 15a In some embodiments, R 1 is a halogen, C1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R is optionally substituted with one, two, or three groups selected from alkoxyl. 1 is oxo, -CN, amino, OH, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyl, and C 3-6 Optionally substituted with one, two, or three groups selected from cycloalkyl.

[0293] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0294] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15aIn some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9 Heteroaryl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0295] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted. 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl; 1-9In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R is heteroaryl, and pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted. 1 is unsubstituted pyrazolyl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted imidazolyl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridinyl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted thiazolyl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.

[0296] In some embodiments of the compound of Formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0297] [ka] In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1 teeth,

[0298] [ka] each of which is selected from 1, 2, or 3 R 15a In some embodiments, R 1 teeth

[0299] [ka] In some embodiments, R 1 teeth

[0300] [ka] In some embodiments, R 1 teeth

[0301] [ka] In some embodiments, R 1 teeth

[0302] [ka] In some embodiments, R 1 teeth

[0303] [ka] In some embodiments, R 1 teeth

[0304] [ka] In some embodiments, R 1 teeth

[0305] [ka] It is.

[0306] Any combination of the above groups for the various variables is contemplated herein. Throughout the specification, groups and substituents thereof will be chosen by one of ordinary skill in the art to provide stable moieties and compounds.

[0307] In some embodiments,

[0308] [ka]

[0309] [ka] Provided herein is a compound selected from:

[0310] In some embodiments, provided herein is a compound, or a pharma- ceutically acceptable salt or solvate thereof, wherein the compound is selected from the compounds of Table 1A.

[0311] [Table 1-1]

[0312] [Table 1-2]

[0313] [Table 1-3]

[0314] [Table 1-4]

[0315] [Table 1-5]

[0316] [Table 1-6]

[0317] [Table 1-7]

[0318] [Table 1-8]

[0319] [Table 1-9]

[0320] [Table 1-10]

[0321] In some embodiments, formula (IV)

[0322] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15c and optionally substituted with one, two, three, or four groups selected from Z 1 is CR 1b or N, Z 2 is CR 2b or N, Z 3 is CR 3bor N, R 1 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15a and optionally substituted with one, two, or three groups selected from R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from Or, R 2b and R 3b Together, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Forming a heteroaryl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15e and optionally substituted with one, two, three, or four groups selected from Each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on adjacent carbons 15e Together, C 2 Forming an alkenylene, Alternatively, two R on the same atom 15e Together, C 3-6 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10, -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on different atoms 15e Together, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are each independently hydrogen, C 1-6 Alkyl, or C 1-6 is haloalkyl, R 12 are each independently hydrogen, C 1-6 Alkyl, or C 1-6 haloalkyl, and R 13 are each independently hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 It is optionally substituted with one, two, or three groups selected from heteroaryl.

[0323] In some embodiments of the compound of Formula (IV), R 2 is C 6-10 Aryl or C 1-9 heteroaryl, each of which is R 15c and optionally substituted with one, two, three, or four groups selected from:

[0324] In some embodiments of the compound of Formula (IV), R 2 is R 15c C optionally substituted with one, two, three, or four groups selected from 1-9 It is heteroaryl.

[0325] In some embodiments of the compound of Formula (IV), R 2 is R 15c and R is a 5- or 6-membered heteroaryl optionally substituted with 1, 2, 3, or 4 groups selected from:

[0326] In some embodiments of the compound of Formula (IV), R 2 is R 15c and R is a 6-membered heteroaryl optionally substituted with 1, 2, 3, or 4 groups selected from:

[0327] In some embodiments of the compound of Formula (IV), R 2 is R 15c and pyridinyl optionally substituted with 1, 2, 3, or 4 groups selected from:

[0328] In some embodiments of the compound of Formula (IV), R 2 is R 15cand R is 1, 2, 3, or 4 groups selected from the group consisting of phenyl,

[0329] In an embodiment of the compound of formula (IV), R 2 teeth,

[0330] [ka] It is.

[0331] In some embodiments of the compound of formula (IV), Z 1 is CR 1b and Z 2 is CR 2b and Z 3 is CR 3b It is.

[0332] In some embodiments of the compound of formula (IV), Z 1 is N, Z 2 is CR 2b and Z 3 is CR 3b It is.

[0333] In some embodiments of the compound of formula (IV), Z 1 is CR 1b and Z 2 is N, and Z 3 is CR 3b It is.

[0334] In some embodiments of the compound of formula (IV), Z 1 is CR 1b and Z 2 is CR 2b and Z 3is N.

[0335] In some embodiments of the compound of Formula (IV), R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 ) and C 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from:

[0336] In some embodiments of the compound of Formula (IV), R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 and C 1-6 Alkyl, C 3-6 Cycloalkyl, and C 2-9 Heterocycloalkyl is R 15b and optionally substituted with one, two, or three groups selected from:

[0337] In some embodiments of the compound of Formula (IV), R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 3-6 Cycloalkyl, -OR 10 , -SR 10 , or -SF 5 and C 3-6 Cycloalkyl is R 15b and optionally substituted with one, two, or three groups selected from:

[0338] In some embodiments of the compound of Formula (IV), R 1b , R 2b , and R 3b are independently hydrogen, halogen, -OR 10 , -SR 10 , or -SF 5 It is.

[0339] In some embodiments of the compound of Formula (IV), R 1b , R 2b , and R 3b are independently hydrogen or -OR 10 It is.

[0340] In some embodiments of the compound of Formula (IV), R 1b , R 2b , and R 3b is hydrogen.

[0341] In some embodiments of the compound of Formula (IV), R 1b is hydrogen.

[0342] In some embodiments of the compound of Formula (IV), R 2b and R 3b Together, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Forming a heteroaryl, C 3-6 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15e and optionally substituted with one, two, three, or four groups selected from:

[0343] In some embodiments of the compound of Formula (IV), R 2b and R 3b Together, C 3-6 Cycloalkyl or C 2-9 Forming a heterocycloalkyl, C 3-6 Cycloalkyl and C 2-9 Heterocycloalkyl is R 15e and optionally substituted with one, two, three, or four groups selected from:

[0344] In some embodiments of the compound of Formula (IV), R 2b and R 3b Together, R 15e C optionally substituted with one, two, three, or four groups selected from 2-9 Forms a heterocycloalkyl.

[0345] In some embodiments of the compound of Formula (IV), R 2b and R 3b Together, R 15e C optionally substituted with one, two, three, or four groups selected from 2-6 Forms a heterocycloalkyl.

[0346] In some embodiments of the compound of Formula (IV), R 2b and R 3b Together, R 15e C optionally substituted with one, two, three, or four groups selected from 6-9 Forms a heterocycloalkyl.

[0347] In some embodiments of the compound of Formula (IV), R 2b and R 3band R are taken together to form a 5-7 membered heterocycloalkyl containing 1 or 2 heteroatoms selected from O and N. In some embodiments of the compound of formula (IV), R 2b and R 3b taken together form a 6-membered heterocycloalkyl containing one heteroatom which is O.

[0348] In some embodiments of the compound of Formula (IV), R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 ).

[0349] In some embodiments of the compound of Formula (IV), R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, or C 1-6 It is haloalkyl.

[0350] In some embodiments of the compound of Formula (IV), R 15e are each independently halogen, oxo, or C 1-6 Alkyl, or C 1-6 It is haloalkyl.

[0351] In some embodiments of the compound of Formula (IV), two R 15e Together, C 2 Forming an alkenylene.

[0352] In some embodiments of the compound of formula (IV), two R 15e Together, C 3-6 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0353] In some embodiments of the compound of formula (IV), two R 15e are taken together as halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , and -N(R 10 )(R 11 C optionally substituted with one, two, or three groups independently selected from 3-6 Forms a cycloalkyl.

[0354] In some embodiments of the compound of formula (IV), two R 15e Together, C 3-6 Forms a cycloalkyl.

[0355] In some embodiments of the compound of Formula (IV), two R 15e Together, C 3-6 Cycloalkyl or C 2-9heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0356] In some embodiments of the compound of Formula (IV), two R 15e are taken together as halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , and -N(R 10 )(R 11 C optionally substituted with one, two, or three groups independently selected from 3-6 Forms a cycloalkyl.

[0357] In some embodiments of the compound of Formula (IV), two R 15e Together, C 3-6 Forms a cycloalkyl.

[0358] In some embodiments of the compound of Formula (IV), R 2b and R 3b In unison,

[0359] [ka] Form.

[0360] In some embodiments of the compound of Formula (IV), R 1 is C 6-10 Aryl or C 1-9 heteroaryl, each of which is R 15aand optionally substituted with one, two, or three groups selected from:

[0361] In some embodiments of the compound of Formula (IV), R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 It is heteroaryl.

[0362] In some embodiments of the compound of Formula (IV), R 1 is R 15a and R is a 5- or 6-membered heteroaryl optionally substituted with one, two, or three groups selected from:

[0363] In some embodiments of the compound of Formula (IV), R 1 is R 15a is a 5-membered heteroaryl optionally substituted with one, two, or three groups selected from:

[0364] In some embodiments of the compound of Formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is optionally replaced by C 1-9 In some embodiments of the compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5- or 6-membered heteroaryl. In some embodiments of the compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5-membered heteroaryl. In some embodiments of the compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 6-membered heteroaryl. In some embodiments of the compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is monocyclic heteroaryl. In some embodiments of the compound of formula (III), or a pharma- ceutically acceptable salt or solvate thereof, R 1is a bicyclic heteroaryl. In some embodiments, R 1 is R 15a In some embodiments, R 1 is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R is optionally substituted with one, two, or three groups selected from alkoxyl. 1 is oxo, -CN, amino, OH, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyl, and C 3-6 Optionally substituted with one, two, or three groups selected from cycloalkyl.

[0365] In some embodiments of the compound of Formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0366] In some embodiments of the compound of Formula (IV), R 1 is selected from pyrazolyl and thiazolyl 1-9 Heteroaryl, pyrazolyl and thiazolyl are R 15a and optionally substituted with one, two, or three groups selected from:

[0367] In some embodiments of the compound of Formula (IV), R 1 is R 15a and n is 0, 1 or 2.

[0368] In some embodiments of the compound of Formula (IV), R1 is R 15a and R is an optionally substituted pyrazolyl group selected from

[0369] In some embodiments of the compound of Formula (IV), R 1 teeth

[0370] [ka] It is.

[0371] In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R11 In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0372] In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c is independent, C 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of Formula (IV), each R 15a , each R 15b , and each R 15c are independent, -OR 10 It is.

[0373] In some embodiments of the compound of Formula (IV), R 15a are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15a are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15a are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15a are each independently a halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15a are each independently a halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15a are each independently 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15a are each independently 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (IV), R 15a are each independently 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of formula (IV), R15a are each independently -OR 10 It is.

[0374] In some embodiments of the compound of Formula (IV), R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15b are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C3-10 Cycloalkyl, or -OR 10 It is.

[0375] In some embodiments of the compound of Formula (IV), R 15b are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15b are each independently a halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15b are each independently a halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15b are each independently 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15b are each independently 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (IV), R 15b are each independently 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of formula (IV), R 15b are each independently -OR 10 It is.

[0376] In some embodiments of the compound of Formula (IV), R 15c are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15c are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15c are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (IV), R 15c are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0377] In some embodiments of the compound of Formula (IV), R 15c are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15c are each independently a halogen, C 1-6 Alkyl, C3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15c are each independently a halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15c are each independently 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (IV), R 15c are each independently 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (IV), R 15c are each independently 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of formula (IV), R 15c are each independently -OR 10 It is.

[0378] In some embodiments, formula (V)

[0379] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is R 15c C optionally substituted with one, two, three, or four groups selected from 1-9 is heteroaryl, Z 1 is CR 1b or N, R 1 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15aand optionally substituted with one, two, or three groups selected from R 1b is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 ,-SCIENCE FICTION 5 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is R 15b and optionally substituted with one, two, or three groups selected from X is -C(R 6 )(R 6a )-, -S-, -O-, or -N(R 7 )-and R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; Or, R 6 and R 6a come together to form oxo, R 7 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; Ring A is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 is heteroaryl, Each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from R 15e are each independently halogen, oxo, -CN, C1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R13 , -CH 2 S(O) 2 R 13 , or -CH 2 S(O) 2 N(R 10 )(R 11 ) and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O)2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on adjacent carbons 15e Together, C 2 Forming an alkenylene, Alternatively, two R on the same atom 15e Together, C 3-6 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from Alternatively, two R on different atoms 15e Together, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(O)(NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 Optionally substituted with 1, 2, or 3 groups independently selected from n is 0 to 6; R 10 are hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; R 11 are hydrogen, C 1-6 Alkyl, or C 1-6 is haloalkyl, R 12 are hydrogen, C 1-6 Alkyl, or C 1-6 haloalkyl, and R 13 are hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 Heteroaryl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, hydroxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 It is optionally substituted with one, two, or three groups selected from heteroaryl.

[0380] In some embodiments of the compound of Formula (V), R 2 is R 15cand R is a 5- or 6-membered heteroaryl optionally substituted with 1, 2, 3, or 4 groups selected from:

[0381] In some embodiments of the compound of Formula (V), R 2 is R 15c and R is a 6-membered heteroaryl optionally substituted with 1, 2, 3, or 4 groups selected from:

[0382] In some embodiments of the compound of Formula (V), R 2 is R 15c and pyridinyl optionally substituted with 1, 2, 3, or 4 groups selected from:

[0383] In an embodiment of the compound of formula (V), R 2 teeth,

[0384] [ka] It is.

[0385] In some embodiments of the compound of Formula (V), ring A is C 3-6 Cycloalkyl or C 2-9 It is a heterocycloalkyl.

[0386] In some embodiments of the compound of Formula (V), ring A is C 2-9 It is a heterocycloalkyl.

[0387] In some embodiments of the compound of Formula (V), ring A is C 2-6 It is a heterocycloalkyl.

[0388] In some embodiments of the compound of Formula (V), ring A is C 6-9In some embodiments of the compound of formula (V), ring A is a 6-membered heterocycloalkyl. In some embodiments of the compound of formula (V), ring A is a 5-7 membered heterocycloalkyl containing one or two heteroatoms selected from O and N. In some embodiments of the compound of formula (V), ring A is a 6 membered heterocycloalkyl containing one heteroatom that is O.

[0389] In some embodiments of the compound of Formula (V), R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 ).

[0390] In some embodiments of the compound of Formula (V), R 15e are each independently halogen, oxo, -CN, C 1-6 Alkyl, or C 1-6 It is haloalkyl.

[0391] In some embodiments of the compound of Formula (V), R 15e are each independently halogen, oxo, or C 1-6 Alkyl, or C 1-6 It is haloalkyl.

[0392] In some embodiments of the compound of Formula (V), two R 15e Together, C 2 Forming an alkenylene.

[0393] In some embodiments of the compound of Formula (V), two R 15e Together, C 3-6 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0394] In some embodiments of the compound of Formula (V), two R 15e are taken together as halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , and -N(R 10 )(R 11 C optionally substituted with one, two, or three groups independently selected from 3-6 Forms a cycloalkyl.

[0395] In some embodiments of the compound of Formula (V), two R 15e Together, C 3-6 Forms a cycloalkyl.

[0396] In some embodiments of the compound of Formula (V), two R 15e Together, C 3-6Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with 1, 2, or 3 groups independently selected from

[0397] In some embodiments of the compound of Formula (V), two R 15e are taken together as halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 10 , and -N(R 10 )(R 11 C optionally substituted with one, two, or three groups independently selected from 3-6 Forms a cycloalkyl.

[0398] In some embodiments of the compound of Formula (V), two R 15e Together, C 3-6 Forms a cycloalkyl.

[0399] In some embodiments of the compound of Formula (V), n is 0 to 4. In some embodiments of the compound of Formula (V), n is 2 to 4. In some embodiments of the compound of Formula (V), n is 2. In some embodiments of the compound of Formula (V), n is 1 or 2. In some embodiments of the compound of Formula (V), n is 1. In some embodiments of the compound of Formula (V), n is 1 to 3.

[0400] In some embodiments of the compound of Formula (V),

[0401] [ka] teeth,

[0402] [ka] It is.

[0403] In some embodiments of the compound of Formula (V), Z 1 is N. In some embodiments of the compound of Formula (V), Z 1 is CR 1b It is.

[0404] In some embodiments of the compound of Formula (V), R 1b is hydrogen or halogen. In some embodiments of the compound of formula (V), R 1b is hydrogen.

[0405] In some embodiments of the compound of Formula (V), X is -C(R 6 )(R 6a In some embodiments of the compound of formula (V), X is -C(R 6 )(R 6a In some embodiments of the compound of Formula (V), X is -C(R 6 )(R 6a In some embodiments of the compound of Formula (V), X is -O-. In some embodiments of the compound of Formula (V), X is -S-. In some embodiments of the compound of Formula (V), X is -N(R 7 In some embodiments of the compound of Formula (V), X is -S-, -O-, or -N(R 7 )-.

[0406] In some embodiments of the compound of Formula (V), R 6 and R 6a are independently hydrogen, halogen, C 1-6 Alkyl, or C 1-6In some embodiments of the compound of formula (V), R 6 and R 6a are independently hydrogen or C 1-6 In some embodiments of the compound of formula (V), R 6 and R 6a is hydrogen. In some embodiments of the compound of Formula (V), R 6 and R 6a together form oxo.

[0407] In some embodiments of the compound of Formula (V), R 7 is hydrogen, C 1-6 Alkyl, or C 1-6 In some embodiments of the compound of formula (V), R 7 is hydrogen or C 1-6 In some embodiments of the compound of formula (V), R 7 is hydrogen.

[0408] In some embodiments of the compound of Formula (V), R 1 is C 6-10 Aryl or C 1-9 heteroaryl, each of which is R 15a and optionally substituted with one, two, or three groups selected from:

[0409] In some embodiments of the compound of Formula (V), R 1 is R 15a C optionally substituted with one, two, or three groups selected from 1-9 It is heteroaryl.

[0410] In some embodiments of the compound of Formula (V), R 1 is R 15a and R is a 5- or 6-membered heteroaryl optionally substituted with one, two, or three groups selected from:

[0411] In some embodiments of the compound of Formula (V), R1 is R 15a is a 5-membered heteroaryl optionally substituted with one, two, or three groups selected from:

[0412] In some embodiments of the compound of Formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is optionally replaced by C 1-9 In some embodiments of the compound of formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5- or 6-membered heteroaryl. In some embodiments of the compound of formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5-membered heteroaryl. In some embodiments of the compound of formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 6-membered heteroaryl. In some embodiments of the compound of formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is monocyclic heteroaryl. In some embodiments of the compound of formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is a bicyclic heteroaryl. In some embodiments, R 1 is R 15a In some embodiments, R 1 is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R is optionally substituted with one, two, or three groups selected from alkoxyl. 1 is oxo, -CN, amino, OH, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyl, and C 3-6 Optionally substituted with one, two, or three groups selected from cycloalkyl.

[0413] In some embodiments of the compound of Formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a In some embodiments of the compound of formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1 is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 In some embodiments of the compound of formula (V), or a pharma- ceutically acceptable salt or solvate thereof, R 1is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl; 1-9 Heteroaryl, including pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, is R 15a and R 15a is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and -OR 10 is selected from.

[0414] In some embodiments of the compound of Formula (V), R 1 is selected from pyrazolyl and thiazolyl 1-9 Heteroaryl, pyrazolyl and thiazolyl are R 15a and optionally substituted with one, two, or three groups selected from:

[0415] In some embodiments of the compound of Formula (V), R 1 is R 15a and n is 0, 1 or 2.

[0416] In some embodiments of the compound of Formula (V), R 1 is R 15a and R is an optionally substituted pyrazolyl group selected from

[0417] In some embodiments of the compound of Formula (V), R 1 teeth

[0418] [ka] In some embodiments of the compound of formula (V), R 1 teeth

[0419] [ka] It is.

[0420] In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0421] In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c is independent, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c is independent, C 3-10Cycloalkyl or -OR 10 In some embodiments of the compound of Formula (V), each R 15a , each R 15b , and each R 15c are independent, -OR 10 It is.

[0422] In some embodiments of the compound of Formula (V), R 15a are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of formula (V), R 15a are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (V), R 15a are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11In some embodiments of the compound of formula (V), R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15a are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15a are each independently a halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15a are each independently a halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15a are each independently 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15a are each independently 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), R 15a are each independently 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), R 15a are each independently -OR 10 It is.

[0423] In some embodiments of the compound of Formula (V), R 15a are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2-C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of formula (V), R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (V), R 15b are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (V), R 15b are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0424] In some embodiments of the compound of Formula (V), R 15b are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R15b are each independently a halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15b are each independently a halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15b are each independently 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15b are each independently 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), R 15b are each independently 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), R 15b are each independently -OR 10 It is.

[0425] In some embodiments of the compound of Formula (V), R 15c are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -CH 2 -C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, C 1-9 Heteroaryl, -CH 2 -C 1-9 Heteroaryl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10, -C(O)R 13 , or -C(O)N(R 10 )(R 11 In some embodiments of the compound of formula (V), R 15c are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (V), R 15c are each independently halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments of the compound of formula (V), R 15c are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl, or -OR 10 It is.

[0426] In some embodiments of the compound of Formula (V), R 15c are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15c are each independently a halogen, C 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15c are each independently a halogen, C 1-6 Alkyl, or -OR 10 In some embodiments of the compound of formula (V), R 15c are each independently 1-6 Alkyl, C 3-10 Cycloalkyl, or -OR10 In some embodiments of the compound of formula (V), R 15c are each independently 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), R 15c are each independently 3-10 Cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), R 15c are each independently -OR 10 It is.

[0427] In some embodiments, formula (VI)

[0428] [ka] or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl, each of which is R 15c and optionally substituted with one, two, three, or four groups selected from Z 1 is CR 1b or N, R 1 is C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, or C 1-9 heteroaryl...

Claims

1. Formula (I') 【Chemistry 1】 or a pharmaceutically acceptable salt thereof, wherein Y 1 is CR 1a or N; Y 2 is CR 2a or N; Y 3 is CR 3a or N; Y 4 is CR 4a or N; Y 5 is CR 5a or N; Z 1 is CR 1b or N; Z 2 is CR 2b or N; Z 3 is CR 3b or N; X is —O— or —S—; or when X is selected from —C(R 6 )(R 6a )— and —N(R 7 )—, at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N; R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ; R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b and R 3b independently represent hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, —OR 10 , —SR 10 , —SF 5 , —N(R 10 )(R 11 ), —C(O)OR 10 , —OC(O)N(R 10 )(R 11 ), —N(R 12 )C(O)N(R 10 )(R 11 ), —N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R 13 , -CH 2 S(O) 2 R 13 and —CH 2 S(O) 2 N(R 10 )(R 11 ), wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with 1, 2, or 3 groups selected from R 15b ; each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with 1, 2, or 3 groups selected from halogen, —CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl; each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl; each R 13 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with 1, 2, or 3 groups selected from halogen, —CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and Each R 15a and each R 15b is independently halogen, oxo, —CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, —CH 2 —C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, —CH 2 —C 2-9 heterocycloalkyl, C 6-10 aryl, —CH 2 —C 6-10 aryl, C 1-9 heteroaryl, —CH 2 —C 1-9 heteroaryl, —OR 10 , —SR 10 , —N(R 10 )(R 11 ), —C(O)OR 10 , —OC(O)N(R 10 )(R 11 ), —N(R 12 )C(O)N(R 10 ) (R 11 ), -N(R 12 )C(O)OR 13 , -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 and N(R 12 )C(O)R 13 , —CH 2 S(O) 2 R 13 , and —CH 2 S(O) 2 N(R 10 )(R 11 ), wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, —CH 2 —C 3-10 cycloalkyl, C 2-9 heterocycloalkyl, —CH 2 —C 2-9 heterocycloalkyl, C 6-10 aryl, —CH 2 —C 6-10 aryl, —CH 2 —C 1-9 heteroaryl, and C 1-9 heteroaryl are selected from halogen, oxo, —CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, —OR 10 , -SR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 12 )C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)OR 13, -N(R 12 )S(O) 2 R 13 , -C(O)R 13 , -S(O)R 13 , -OC(O)R 13 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 12 )C(O)R 13 , -S(O) 2 R 13 , -S(O) 2 N(R 10 )(R 11 )-, S(=O)(=NH)N(R 10 )(R 11 ), -CH 2 C(O)N(R 10 )(R 11 ), -CH 2 N(R 12 )C(O)R, or a pharmaceutically acceptable salt thereof, optionally substituted with one, two, or three groups independently selected from:

2. Formula (Ia) 【Chemistry 2】 2. The compound of claim 1 having the structure: or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 1a and R 5a are independently selected from hydrogen and —OR 10 , and R 10 is C 1-6 alkyl.

4. Y 2 is N, Y 3 is CR 3a , and 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein Y<4> is CR<4a>.

5. Y 2 is CR 2a , Y 3 is CR 3a , and 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein Y<4> is CR<4a>.

6. R 2a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or —OR 10 ; R 3a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-6 alkynyl, and 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 4a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or —OR 10 .

7. R 2a is hydrogen, R 3a is C 1-6 alkyl, and 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R<4a> is hydrogen.

8. Z 1 is CR 1b , Z 2 is CR 2b , and 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein Z3 is CR3b.

9. Z 1 is CR 1b , Z 2 is CR 2b , and 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein Z3 is N.

10. R 1b is hydrogen, R 2b is hydrogen; R 3b is —OR 10 , and 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 10 is C 1-6 alkyl.

11. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 1 is an optionally substituted 5-membered heteroaryl.

12. R 1 is 【Transformation 3】 3. The compound of claim 2, selected from:

13. R 1 is 【Chemistry 4】 13. The compound of claim 12, wherein:

14. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein X is —O—. 【Request Item 15】 【Chemistry 5-1】 【Chemistry 5-2】 【Chemistry 5-3】 3. The compound of claim 2, selected from the group consisting of: or a pharmaceutically acceptable salt thereof. 【Request Item 16】 【Chemistry 6】 16. The compound of claim 15, which is a compound selected from the group consisting of:

17. A pharmaceutical composition comprising a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

18. Use of a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating cancer.

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