NLRP3 Modulators

Abstract

Described herein are NLRP3 modulators and methods of utilizing the NLRP3 modulators in the treatment of diseases, disorders, or conditions. Also described herein are pharmaceutical compositions comprising such compounds.

Description

[Technical field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 216,446, filed June 29, 2021, and U.S. Provisional Patent Application No. 63 / 320,155, filed March 15, 2022, each of which is incorporated by reference in its entirety. [Background technology]

[0002] The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is a key component of the innate immune response and inflammatory processes, and its aberrant activity is a pathogenesis in genetic disorders such as cryopyrin-associated periodic syndromes (CAPS), as well as complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease, and atherosclerosis. Current treatments for NLRP3-associated diseases include biologic agents that target IL-1. Small molecule inhibitors of NLRP3 offer an attractive alternative to these biologics given their safety, as well as the potential for improved patient comfort and compliance. Summary of the Invention

[0003] In one embodiment, the compound of formula (Ic') or formula (Ij')

[0004] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, or 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 , -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 ), where 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 halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 teeth

[0005] [ka] and R 7a , R 7b , R 7c , R 7d , R 7e , R 7g , and R 7h are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and 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, 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 is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 optionally substituted with one, two, or three groups selected from heteroaryl; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from n is 0, 1, 2, 3, or 4.

[0006] In some embodiments, the formula (Ic')

[0007] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0008] In some embodiments, the compound has formula (Ic'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , R 7e , R 7f , and R 7g is hydrogen.

[0009] In some embodiments, the formula (Ij')

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

[0011] In some embodiments, there is a compound of formula (Ij'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h is hydrogen.

[0012] In another embodiment, the compound of formula (Ig'), (Ih'), or (Ik')

[0013] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ), C(R 7a )(R 7b ), O, S, N, or N(R 8a ) and X is C(R 7c ), C(R 7c )(R 7d ), O, S, N, or N(R 8b ) and Z is C(R 7g ), C(R 7g )(R 7h ), O, S, N, or N(R 8d ) and L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, or C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C2-9 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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 teeth

[0014] [ka] and R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 8a , R 8b , and R 8d are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 10 are each independently 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, 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 is halogen, 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, and 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, wherein 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, 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from n is 0, 1, 2, 3, or 4.

[0015] In some embodiments, the formula (Ig')

[0016] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0017] In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where W is O or S. In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is N or C(H). In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where W is S and Z is C(H).

[0018] In some embodiments, the formula (Ih')

[0019] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0020] In some embodiments, there are compounds of formula (Ih'), or pharma- ceutically acceptable salts or solvates thereof, where W is N or C(H). In some embodiments, there are compounds of formula (Ih'), or pharma- ceutically acceptable salts or solvates thereof, where Z is O or S. In some embodiments, there are compounds of formula (Ih'), or pharma- ceutically acceptable salts or solvates thereof, where W is C(H) and Z is S. In some embodiments, there are compounds of formula (Ig') or (Ih'), or pharma- ceutically acceptable salts or solvates thereof, where X is N or C(H). In some embodiments, there are compounds of formula (Ig') or (Ih'), or pharma- ceutically acceptable salts or solvates thereof, where X is C(H).

[0021] In some embodiments, the formula (Ik')

[0022] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0023] In some embodiments, there is a compound of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where W and Z are N. In some embodiments, there is a compound of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where W and Z are C(H). In some embodiments, there is a compound of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where X is S. In some embodiments, there is a compound of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where X is O.

[0024] In another embodiment, the compound of formula (Im')

[0025] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ) or N, X is C(R 7c ) or N, Z is C(R 7g ) or N, L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 3-8 Cycloalkyl and C 2-9 heterocycloalkyl, wherein C 3-8 Cycloalkyl and C 2-9 Heterocycloalkyl can have one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7c , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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 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, and 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, 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 is halogen, 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 14 and each R 15 are each independently halogen, -CN, or C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6Alkenyl, 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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0026] In some embodiments, the compound is of formula (Im′), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a ), and X is C(R 7c ), and Z is C(R 7g In some embodiments, there is a compound of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, and Z are C(H). In some embodiments, there is a compound of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 2-9 In some embodiments, the compound is of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 and piperidinyl optionally substituted with a group.

[0027] In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0028] [ka] and n is 0. In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0029] [ka] and R 15 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0030] [ka] and R 15 Ha-CH 3 It is.

[0031] In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , or -C(O)N(R 10 )(R 11 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 Alkyl or C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen or C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 2-9 heterocycloalkyl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 2-9 Heterocycloalkyl can have one, two, three, four, or five R 15 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 2-9In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 3-8 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , and -N(R 10 )(R 11 ), wherein C 1-6 Alkyl, C 3-6 Cycloalkyl, and C 2-9 Heterocycloalkyl is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 are each independently a halogen, an unsubstituted C 1-6 Alkyl, and C 1-6In some embodiments, selected from haloalkyl, the compound is of Formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(R 9c In some embodiments, a compound of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(H)-. In some embodiments, a compound of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -O-.

[0032] In another embodiment, the compound of formula (I)

[0033] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, U is C, CH, or N; V is C, CH, or N; W is C(R 7a ), C(R 7a )(R 7b ), O, S, N, or N(R 8a ) and X does not exist or C(R 7c ), C(R 7c )(R 7d ), O, S, N, or N(R 8b ) and Y does not exist or C(R 7e ), C(R 7e )(R 7f ), O, S, N, or N(R 8c ) and Z is C(R 7g ), C(R 7g )(R 7h ), O, S, N, or N(R 8d ) and L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h are each independently hydrogen, halogen, -CN, or 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 7b and R 7h combine to form a cycloalkyl or heterocycloalkyl ring; R 8a , R 8b , R 8c , and R 8d are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; or R 8a and R 7h are combined to form a heterocycloalkyl ring; or R 8d and R 7b are combined to form a heterocycloalkyl ring; R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, 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, and 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, 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 is halogen, 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from

[0034] [ka] indicates a single or double bond such that all valences are satisfied.

[0035] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where V is C. In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where U is C.

[0036] In some embodiments, the compound of formula (Ia)

[0037] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0038] In some embodiments, the compound of formula (Ib)

[0039] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0040] In some embodiments, the formula (Ic)

[0041] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0042] In some embodiments, the compound of formula (Id)

[0043] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0044] In some embodiments, the compound of formula (Ie)

[0045] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0046] In some embodiments, there is a compound of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h is hydrogen. In some embodiments, there is a compound of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , R 7e , R 7f , and R 7g is hydrogen, and R7b and R 7h are combined to form a cycloalkyl ring. In some embodiments, there is a compound of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , R 7e , R 7f , and R 7g is hydrogen, and R 7b and R 7h are combined to form a heterocycloalkyl ring.

[0047] In some embodiments, the formula (If)

[0048] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0049] In some embodiments, the formula (Ig)

[0050] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0051] In some embodiments, there is a compound of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where W is O or S. In some embodiments, there is a compound of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where Z is N or C(H).

[0052] In some embodiments, the compound of formula (Ih)

[0053] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0054] In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where W is N or C(H). In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where Z is O or S. In some embodiments, there are compounds of formula (Ig) or (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where X is N or C(H).

[0055] In some embodiments, the compound of formula (Ii)

[0056] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0057] In some embodiments, the compound is of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is O, Z is O, and X is C(R 7c )(R 7d In some embodiments, the compound is of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(F). 2 It is.

[0058] In some embodiments, the compound of formula (Ij)

[0059] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0060] In some embodiments, there is a compound of formula (Ij), or a pharma- ceutically acceptable salt or solvate thereof, wherein R7a , R 7b , R 7c , R 7d , R 7g , and R 7h is hydrogen.

[0061] In some embodiments, the formula (Ik)

[0062] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0063] In some embodiments, there is a compound of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where W and Z are N. In some embodiments, there is a compound of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where W and Z are C(H). In some embodiments, there is a compound of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where X is S. In some embodiments, there is a compound of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where X is O.

[0064] In some embodiments, the formula (Im)

[0065] [ka] or a pharma- ceutically acceptable salt or solvate thereof.

[0066] In some embodiments, the compound is of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a ), and X is C(R 7c ), and Z is C(R 7gIn some embodiments, there is a compound of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, and Z are C(H).

[0067] In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , or -C(O)N(R 10 )(R 11 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 Alkyl or C 1-6 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen or C 1-6 In some embodiments, the compounds are of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 2-9 heterocycloalkyl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 2-9 Heterocycloalkyl can have one, two, three, four, or five R 15 In some embodiments, the compounds are of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 2-9In some embodiments, the compounds are of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 3-8 In some embodiments, there is a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 1-6 In some embodiments, the compounds are of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , and -N(R 10 )(R 11 ), wherein C 1-6 Alkyl, C 3-6 Cycloalkyl, and C 2-9 Heterocycloalkyl is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11In some embodiments, the compounds are of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 are each independently a halogen, an unsubstituted C 1-6 Alkyl, and C 1-6 In some embodiments selected from haloalkyl, there is a compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein: L is -N(R 9c )-. In some embodiments, there is a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(H)-. In some embodiments, there is a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -O-. In some embodiments, there is a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -C(O)-. In some embodiments, there is a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -C(R 9a )(R 9bIn some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a is hydrogen, halogens, and C 1-6 In some embodiments, the compounds are of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9b is selected from hydrogen, halogen, and -OH.

[0068] In another aspect, described herein is a pharmaceutical composition comprising a compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, and a pharma- ceutically acceptable excipient.

[0069] In some embodiments, described herein is a method of treating a metabolic disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, described herein is a method of treating a metabolic disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein the metabolic disease is selected from type 2 diabetes, atherosclerosis, obesity, and gout.

[0070] In some embodiments, described herein is a method of treating liver disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, described herein is a method of treating liver disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein the liver disease is selected from nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), viral hepatitis, and cirrhosis.

[0071] In some embodiments, described herein is a method of treating a pulmonary disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, described herein is a method of treating a pulmonary disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein the pulmonary disease is selected from asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis.

[0072] In some embodiments, described herein is a method of treating a central nervous system disorder in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, described herein is a method of treating a central nervous system disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein the central nervous system disease is selected from Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, traumatic brain injury, ischemic stroke and reperfusion, hemorrhagic stroke, epilepsy, and depression.

[0073] In some embodiments, described herein is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, described herein is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein the inflammatory or autoimmune disease is selected from rheumatoid arthritis, multiple sclerosis, psoriasis, lupus, inflammatory bowel disease, Crohn's disease, and ulcerative colitis.

[0074] In some embodiments, described herein is a method of treating a cardiovascular disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, described herein is a method of treating a cardiovascular disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein the cardiovascular disease is atherosclerosis or stroke.

[0075] 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 herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0076] definition In the context of this disclosure, a number of terms will be utilized.

[0077] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter belongs. In the event of multiple definitions for terms herein, the definitions in this section prevail. All patents, patent applications, publications, and published nucleotide and amino acid sequences (e.g., sequences available in databases such as GenBank) cited herein are incorporated by reference. When a URL or other such identifier or address is mentioned, it is understood that such identifiers can change and particular information on the Internet may come and go, but equivalent information can be found by an Internet search. Reference thereto acknowledges the availability and public dissemination of such information.

[0078] It is understood that the foregoing general description and the following detailed description are merely exemplary and illustrative and are not restrictive of the claimed subject matter. In this application, the use of the singular includes the plural unless expressly stated otherwise. It is noted that, in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. In this application, the use of "or" means "and / or" unless expressly stated otherwise. Furthermore, the use of the term "including" is non-limiting, as are other forms such as "include," "includes," "included," and the like.

[0079] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0080] Definitions of standard chemical terms can be found in references including, but not limited to, Carey and Sundberg "Advanced Organic Chemistry 4th Ed." Vols. A(2000)and B(2001), Plenum PreS, New York. Unless otherwise specified, conventional methods are mass spectroscopy, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques, and pharmacology.

[0081] Unless specific definitions are provided, the terminology utilized in connection with analytical chemistry, organic synthetic chemistry, and medicinal and pharmaceutical chemistry described herein, and the laboratory methods and techniques thereof, are art-recognized. Standard techniques may be used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation, and delivery, and patient treatment. Standard techniques may be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, lipofection). Reaction and purification techniques may be performed, for example, using kits per manufacturer's specifications, or as commonly accomplished in the art, or as described herein. The foregoing techniques and procedures may be performed in a generally conventional manner, as well as as described in various general and specific references cited and discussed throughout this specification.

[0082] It is to be understood that the methods and compositions described herein are not limited to the specific methodologies, protocols, cell lines, constructs, and reagents described herein, and thus may vary. Moreover, the terminology used herein is intended to describe specific embodiments only, and is not intended to limit the scope of the methods, compounds, and compositions described herein.

[0083] As used herein, C 1 -C x is C 1 -C 2 , C 1 -C 3 ...C 1-C x Includes: C 1 -C x refers to the number of carbon atoms that make up the moiety it designates (excluding any substituents).

[0084] An "alkyl" group refers to a straight or branched hydrocarbon chain radical, containing no unsaturation, consisting solely of carbon and hydrogen atoms. In some embodiments, an "alkyl" group can have 1 to 6 carbon atoms (wherever alkyl appears herein, a number range such as "1 to 6" refers to each integer in the given range. For example, "1 to 6 carbon atoms" means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to a maximum of 6 carbon atoms, although this definition also encompasses occurrences of the term "alkyl" without any number range specified). The alkyl groups of the compounds described herein are defined as "C 1 -C 6 Alkyl" or a similar designation. 1 -C 6 "Alkyl" indicates that the alkyl chain has 1 to 6 carbon atoms, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, iso-pentyl, neo-pentyl, and hexyl. Alkyl groups can be substituted or unsubstituted. Depending on the structure, alkyl groups can be monoradicals or diradicals (i.e., alkylene groups).

[0085] "Alkoxy" refers to the group "-O-alkyl", where alkyl is as defined herein.

[0086] The term "alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms containing at least one carbon-carbon double bond. A non-limiting example of an alkenyl group is -CH=CH 2 , -C(CH 3 )=CH 2 , -CH=CHCH 3 , -CH=C(CH3 ) 2 , and -C(CH 3 )=CHCH 3 In some embodiments, an alkenyl group can have 2 to 6 carbons. An alkenyl group can be substituted or unsubstituted. Depending on the structure, an alkenyl group can be a monoradical or a diradical (i.e., an alkenylene group).

[0087] The term "alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms containing at least one carbon-carbon triple bond. Non-limiting examples of alkynyl groups include -C≡CH, -C≡CCH 3 , -C≡CCH 2 CH 3 , and -C≡CCH 2 CH 2 CH 3 In some embodiments, an alkynyl group can have 2 to 6 carbons. An alkynyl group can be substituted or unsubstituted. Depending on the structure, an alkynyl group can be a monoradical or a diradical (i.e., an alkynylene group).

[0088] "Amino" is -NH 2 Refers to the base.

[0089] The term "alkylamine" or "alkylamino" refers to -N(alkyl) x H y "Dialkylamino" refers to the -N(alkyl) group, where alkyl is as defined herein, and x and y are selected from the group x=1, y=1, and x=2, y=0. When x=2, the alkyl groups together with the nitrogen to which they are attached can optionally form a cyclic ring system. "Dialkylamino" refers to -N(alkyl) 2 refers to the group, where alkyl is as defined herein.

[0090] The term "aromatic" refers to a planar ring having a delocalized π-electron system containing 4n+2 π electrons, where n is an integer. Aromatic rings can be formed from 5, 6, 7, 8, 9, or more than 9 atoms. Aromatics can be optionally substituted. The term "aromatic" includes both aryl (e.g., phenyl, naphthalenyl) and heteroaryl (e.g., pyridinyl, quinolinyl) groups.

[0091] As used herein, the term "aryl" refers to an aromatic ring in which each of the atoms forming the ring is a carbon atom. An aryl ring can be formed by 5, 6, 7, 8, 9, or more than 9 carbon atoms. An aryl group can be optionally substituted. Examples of aryl groups include, but are not limited to, phenyl and naphthalenyl. Depending on the structure, an aryl group can be a monoradical or a diradical (i.e., an arylene group).

[0092] "Carboxy" is -CO 2 H. In some embodiments, the carboxy moiety may be replaced with a "carboxylic acid bioisostere," which refers to a functional group or moiety that exhibits similar physical and / or chemical properties as a carboxylic acid moiety. A carboxylic acid bioisostere has similar biological properties as a carboxylic acid group. A compound that includes a carboxylic acid moiety can have the carboxylic acid moiety replaced with a carboxylic acid bioisostere and have similar physical and / or biological properties compared to a compound that includes a carboxylic acid. For example, in one embodiment, the carboxylic acid bioisostere will ionize at physiological pH to about the same extent as a carboxylic acid group. Examples of carboxylic acid bioisosteres include, but are not limited to, the following:

[0093] [ka]

[0094] The term "cycloalkyl" refers to a monocyclic or polycyclic non-aromatic radical, where each of the atoms forming the ring (i.e., skeletal atoms) is a carbon atom. A cycloalkyl can be saturated or partially unsaturated. A cycloalkyl can be fused with an aromatic ring (in which case the cycloalkyl is attached through a non-aromatic ring carbon atom). In some embodiments, cycloalkyl groups include groups having 3 to 10 ring atoms.

[0095] The terms "heteroaryl" or, alternatively, "heteroaromatic" refer to an aryl group that contains one or more ring heteroatoms selected from nitrogen, oxygen, and sulfur. An N-containing "heteroaromatic" or "heteroaryl" moiety refers to an aromatic group in which at least one of the skeletal atoms of the ring is a nitrogen atom.

[0096] A "heterocycloalkyl" or "heteroalicyclic" group refers to a cycloalkyl group in which at least one skeletal ring atom is a heteroatom selected from nitrogen, oxygen, and sulfur. The radical may be fused with an aryl or heteroaryl. The term heteroalicyclic also includes all cyclic forms of carbohydrates, including but not limited to monosaccharides, disaccharides, and oligosaccharides. Unless otherwise specified, a heterocycloalkyl has 2-10 carbons in the ring. When referring to the number of carbon atoms in a heterocycloalkyl, it is noted that the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including the heteroatom) that make up the heterocycloalkyl (i.e., the skeletal atoms of the heterocycloalkyl ring).

[0097] The term "halo" or alternatively "halogen" means fluoro, chloro, bromo, and iodo.

[0098] The term "haloalkyl" refers to an alkyl group that is substituted with one or more halogens. The halogens can be the same or different. Non-limiting examples of haloalkyl include -CH 2 Cl, -CF 3 , -CHF 2 , -CH 2 CF3 , -CF 2 CF 3 etc.

[0099] The terms "fluoroalkyl" and "fluoroalkoxy" include alkyl and alkoxy groups, respectively, that are substituted with one or more fluorine atoms. A non-limiting example of a fluoroalkyl is -CF 3 , -CHF 2 , -CH 2 F, -CH 2 CF 3 , -CF 2 CF 3 , -CF 2 CF 2 CF 3 , -CF(CH 3 ) 3 A non-limiting example of a fluoroalkoxy group is -OCF 3 , -OCHF 2 , -OCH 2 F, -OCH 2 CF 3 , -OCF 2 CF 3 , -OCF 2 CF 2 CF 3 , -OCF(CH 3 ) 2 etc.

[0100] The term "heteroalkyl" refers to an alkyl radical in which one or more skeletal atoms are selected from atoms other than carbon, such as oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof. The heteroatom may be placed at any interior position of the heteroalkyl group. Examples include, but are not limited to, -CH 2 -O-CH 3 , -CH 2 -CH 2 -O-CH 3 , -CH 2 -NH-CH 3 , -CH 2 -CH 2 -NH-CH 3 , -CH 2 -N(CH 3)-CH 3 , -CH 2 -CH 2 -NH-CH 3 , -CH 2 -CH 2 -N(CH 3 )-CH 3 , -CH 2 -S-CH 2 -CH 3 , -CH 2 -CH 2 -S(O)-CH 3 , -CH 2 -CH 2 -S(O) 2 -CH 3 , -CH 2 -NH-OCH 3 , -CH 2 O-Si(CH 3 ) 3 , -CH 2 -CH=N-OCH 3 , and -CH=CH-N(CH 3 )-CH 3 In addition, up to two heteroatoms may be, for example, -CH 2 -NH-OCH 3 and -CH 2 O-Si(CH 3 ) 3 etc. In addition to the number of heteroatoms, a "heteroalkyl" can have from 1 to 6 carbon atoms.

[0101] The term "bond" or "single bond" refers to a chemical bond between two atoms or two moieties when the atoms connected by the bond are considered to be part of a larger substructure.

[0102] The term "moiety" refers to a specific segment or functional group of a molecule. A chemical moiety is often recognized as a chemical entity embedded in or appended to a molecule.

[0103] As used herein, the substituent "R" appearing alone and without a number designation refers to a substituent selected from among alkyl, haloalkyl, heteroalkyl, alkenyl, cycloalkyl, aryl, heteroaryl (bonded via a ring carbon), and heterocycloalkyl.

[0104] "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes examples when the event or circumstance occurs and examples when it does not occur.

[0105] The term “optionally substituted” or “substituted” refers to any group in which the referenced group is alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, —OH, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, arylsulfone, —CN, alkyne, C 1 -C 6 Alkyl alkyne, halo, acyl, acyloxy, -CO 2 H, -CO 2 -Alkyl, nitro, haloalkyl, fluoroalkyl, and mono- and di-substituted amino groups (e.g., -NH 2 , -NHR, -N(R) 2 ), and protected derivatives thereof. s R s where L s are each independently a bond, -O-, -C(=O)-, -S-, -S(=O)-, or -S(=O) 2 -, -NH-, -NHC(O)-, -C(O)NH-, S(=O) 2 NH-, -NHS(=O) 2 , -OC(O)NH-, -NHC(O)O-, -(C 1 -C 6 alkyl)- or -(C 2 -C 6alkenyl)-, and R s are independently H, (C 1 -C 6 Alkyl), (C 3 -C 8 cycloalkyl), aryl, heteroaryl, heterocycloalkyl, and C 1 -C 6 The protecting groups that may form the protective derivatives of the above substituents can be found in sources such as Greene and Wuts, above.

[0106] As used herein, the term "about" or "approximately" means within 20%, preferably within 10%, and more preferably within 5% of a given value or range.

[0107] The term "therapeutically effective amount," as used herein, refers to an amount of an NLRP3 inhibitor that, when administered to a mammal in need thereof, is effective to at least partially ameliorate or at least partially prevent a disease or disorder described herein.

[0108] As used herein, the term "expression" includes the process by which a polynucleotide is transcribed into mRNA and translated into a peptide, polypeptide, or protein.

[0109] The term "modulate" encompasses either a decrease or an increase in activity or expression, depending on the target molecule.

[0110] The term "activator" is used herein to denote any molecular species that, when administered locally, results in activation of the indicated receptor, regardless of whether the molecular species itself binds to the receptor or whether a metabolic product of the molecular species binds to the receptor. Thus, an activator may be a ligand of the receptor, or it may be an activator that is metabolized to a ligand of the receptor, i.e., a metabolite that is formed in the tissue and is the actual ligand.

[0111] The term "patient" or "mammal" refers to a human, non-human primate, canine, feline, bovine, ovine, porcine, murine, or other veterinary or laboratory mammal. One of skill in the art will recognize that a treatment that reduces the severity of a condition in one species of mammal is predictive of the effectiveness of the treatment in another species of mammal.

[0112] "Pharmaceutically acceptable salt" includes both acid addition salt and base addition salt. The pharmaceutically acceptable salt of any one of the compounds described herein is intended to include all pharmaceutically appropriate salt forms. The preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0113] "Pharmaceutically acceptable acid addition salts" refers to those salts which retain the biological effectiveness and properties of the free base, which are not biologically or otherwise undesirable, and are formed with inorganic acids, such as hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, hydroiodic, hydrofluoric, phosphorous, etc. Also included are salts formed with organic acids, such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids, alkanedioic acids, aromatic acids, aliphatic acids, and aromatic sulfonic acids, and which include, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, etc. Thus, exemplary salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, and the like. Similarly, salts of amino acids such as arginate, gluconate, and galacturonate are contemplated (see, e.g., Berge SM et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1-19 (1997)). Acid addition salts of basic compounds are prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt.

[0114] "Pharmaceutically acceptable base addition salts" refers to those salts that retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared by adding an inorganic or organic base to the free acid. In some embodiments, pharma-ceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Salts derived from organic bases include, but are not limited to, salts of primary amines, secondary amines, tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and base ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N-dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc. See Berge et al., supra.

[0115] As used herein, "treatment" or "treat" or "alleviate" or "ameliorate" are used interchangeably herein. These terms refer to an approach to obtain a beneficial or desired result, including, but not limited to, therapeutic benefit and / or preventive benefit. "Therapeutic benefit" refers to the eradication or amelioration of the underlying disease being treated. Similarly, therapeutic benefit is achieved by the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disease, such that an improvement is observed in the patient, even though the patient still suffers from the underlying disease. For preventive benefit, the composition is administered to a patient at risk of developing a particular disease, or to a patient who reports one or more of the physiological symptoms of a disease, even if the patient has not been diagnosed with the disease.

[0116] NLRP3 Modulators NLRP3 is an intracellular signaling molecule that senses many pathogen-, environmental-, and host-derived factors. Upon activation, NLRP3 binds to apoptosis-associated speck-like proteins that contain a caspase activation and recruitment domain (ASC). ASC then polymerizes to form large aggregates known as ASC specks.

[0117] Polymerized ASC associates with the cysteine ​​protease caspase-1 to form a complex called the inflammasome. This leads to the activation of active caspase-1, which cleaves the precursor forms of the proinflammatory cytokines IL-1β and IL-18 (termed pro-IL-ιβ and pro-IL-18, respectively), thereby activating these cytokines. Caspase-1 further mediates a type of inflammatory cell death known as pyroptosis. ASC speck aggregates can also recruit and activate caspase-8, which can process pro-IL-ιβ and pro-IL-18 and induce apoptotic cell death.

[0118] Caspase-1 cleaves pro-IL-ιβ and pro-IL-18 into their active forms, which are secreted from cells. Active caspase-1 further cleaves gasdermin-D to induce pyroptosis. Caspase-1 further mediates the release of alarmin molecules such as IL-33 and high mobility group box 1 protein (HMGB1) through its control of the pyroptosis cell death pathway. Caspase-1 further cleaves intracellular IL-1R2, leading to its degradation and allowing the release of IL-1a. In human cells, caspase-1 can also control the processing and secretion of IL-37. Several other caspase-i substrates, such as components of the cytoskeleton and glycolytic pathways, may contribute to caspase-I-dependent inflammation.

[0119] NLRP3-dependent ASC specks are released into the extracellular environment where they can activate caspase-1, induce processing of caspase-1 substrates, and propagate inflammation. Active cytokines derived from NLRP3 inflammasome activation are key drivers of inflammation and interact with other cytokine pathways to shape immune responses to infection and injury. For example, IL-ιβ signaling induces secretion of the proinflammatory cytokines IL-6 and TNF. IL-1β and IL-18 synergize with IL-23 to induce IL-17 production by memory CD4 Th17 cells and γδ T cells in the absence of T cell receptor engagement. IL-18 and IL-12 further synergize to induce IFN-γ production from memory T cells and NK cells that drive Th1 responses.

[0120] The inherited CAPS disorders, Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal-onset multisystem inflammatory disease (NOMID), are caused by gain-of-function mutations in NLRP3, thus defining NLRP3 as a key component of the inflammatory process. NLRP3 has also been implicated in the pathogenesis of many complex diseases, including metabolic disorders such as type 2 diabetes, atherosclerosis, obesity, and gout.

[0121] A role for NLRP3 in diseases of the central nervous system is emerging, and lung diseases have also been shown to be affected by NLRP3. In addition, NLRP3 has a role in the development of liver disease, kidney disease, and aging. Many of these associations were defined using NLRP3 KO mice, but insights into the specific activation of NLRP3 in these diseases also exist. In type 2 diabetes (T2D), deposition of islet amyloid polypeptide in the pancreas activates NLRP3 and IL-ιβ signaling, leading to cell death and inflammation.

[0122] Current treatments for NLRP3-related diseases include biologic agents that target IL-1. These are the recombinant IL-1 receptor antagonist anakinra, the neutralizing IL-1β antibody canakinumab, and the soluble decoy IL1 receptor rilonacept. These approaches have proven successful in treating CAPS, and these biologic agents are being used in clinical trials for other IL-1β-related diseases. Small molecule inhibitors of NLRP3 offer an attractive alternative to these biologics, given the potential for improved safety (minimal risk of infection and ease of withdrawal compared to biologics) as well as patient comfort and compliance.

[0123] The compounds of formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im') described herein are NLRP3 modulators. The compounds of formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im') described herein, and compositions comprising these compounds, are useful for the treatment of NLRP3-related diseases, including, but not limited to, type 2 diabetes, atherosclerosis, obesity, and gout.

[0124] In some embodiments, the formula (Ic')

[0125] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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) 2N(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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 teeth

[0126] [ka] and R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, -CN, or 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and 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, 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 is halogen, 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from n is 0, 1, 2, 3, or 4.

[0127] In some embodiments, the compound has formula (Ic'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, or C 1-6 Alkyl, and C 1-6 In some embodiments, the compound is of formula (Ic'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, and C 1-6 In some embodiments, the compound is of formula (Ic'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g is hydrogen.

[0128] In some embodiments, the formula (Ij')

[0129] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 1-9Heteroaryl, -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 ), where 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, C 1-6Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 teeth

[0130] [ka] and R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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 C1-9 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 is halogen, 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, and 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, 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 is halogen, 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from n is 0, 1, 2, 3, or 4.

[0131] In some embodiments, the compound is of formula (Ij'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, or C 1-6 Alkyl, and C 1-6 In some embodiments, the compound is of formula (Ij'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, and C 1-6 In some embodiments, the compounds are of formula (Ij'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R7c , R 7d , R 7g , and R 7h is hydrogen. In some embodiments, there is a compound of formula (Ij'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , and R 7g is hydrogen, and R 7b and R 7h are combined to form a cycloalkyl ring. In some embodiments, there is a compound of formula (Ij'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , and R 7g is hydrogen, and R 7b and R 7h are combined to form a heterocycloalkyl ring.

[0132] In some embodiments, the formula (Ig')

[0133] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a )(R 7b ), O, S, or N(R 8a ) and X is C(R 7c ) or N, Z is C(R 7g ) or N, L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, or C 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 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 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 teeth

[0134] [ka] and R 7a , R 7b , R 7c , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 )(R11 ), -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 8a is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and 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, 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 is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C1-6 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 )(R11 ), -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from n is 0, 1, 2, 3, or 4.

[0135] In some embodiments, there is a compound of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is N(R 8a In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where W is O. In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where W is S. In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(R 7cIn some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(H). In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where X is N. In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(R 7c In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(H). In some embodiments, there are compounds of formula (Ig'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is N.

[0136] In some embodiments, the formula (Ih')

[0137] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ) or N, X is C(R 7c ) or N, Z is C(R 7g )(R 7h ), O, S, or N(R 8d ) and L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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, 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 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 teeth

[0138] [ka] and R 7a , R 7c , R 7g , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 )(R11 ), -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 8d is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and 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, 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 is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C1-6 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 )(R11 ), -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from n is 0, 1, 2, 3, or 4.

[0139] In some embodiments, there is a compound of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is N(R 8d In some embodiments, there are compounds of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is O. In some embodiments, there are compounds of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is S. In some embodiments, there are compounds of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(R 7cIn some embodiments, there are compounds of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(H). In some embodiments, there are compounds of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, where X is N. In some embodiments, there are compounds of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, where W is C(R 7a In some embodiments, there are compounds of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, where W is C(H). In some embodiments, there are compounds of formula (Ih'), or a pharma- ceutically acceptable salt or solvate thereof, where W is N.

[0140] In some embodiments, the formula (Ik')

[0141] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ) or N, X is C(R 7c )(R 7d ), O, S, or N(R 8b ) and Z is C(R 7g ) or N, L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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, 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 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 teeth

[0142] [ka] and R 7a , R 7c , R 7d , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 )(R11 ), -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 8b is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and 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, 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 is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C1-6 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 )(R11 ), -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from n is 0, 1, 2, 3, or 4.

[0143] In some embodiments, the compound is of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a). In some embodiments, there are compounds of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where W is C(H). In some embodiments, there are compounds of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where W is N. In some embodiments, there are compounds of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where X is S or O. In some embodiments, there are compounds of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where X is S. In some embodiments, there are compounds of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where X is O. In some embodiments, there are compounds of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(R 7g In some embodiments, there are compounds of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(H). In some embodiments, there are compounds of formula (Ik'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is N.

[0144] In some embodiments, the formula (Im')

[0145] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ) or N, X is C(R 7c ) or N, Z is C(R 7g ) or N, L is -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5are each independently hydrogen, halogen, -CN, 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 , -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), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 3-8 Cycloalkyl and C 2-9 heterocycloalkyl, wherein C 3-8 Cycloalkyl and C 2-9 Heterocycloalkyl can have one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7c , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-6 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 is halogen, 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, and 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, 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 is halogen, 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 heteroaryl; and Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 2C(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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0146] In some embodiments, the compound is of formula (Im′), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a In some embodiments, there are compounds of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, where W is C(H). In some embodiments, there are compounds of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, where W is N. In some embodiments, there are compounds of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(R 7cIn some embodiments, there are compounds of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(H). In some embodiments, there are compounds of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, where X is N. In some embodiments, there are compounds of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(R 7g In some embodiments, there are compounds of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(H). In some embodiments, there are compounds of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, where Z is N.

[0147] In some embodiments, the compound is of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 2-9 In some embodiments, the compound is of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, the compound is of formula (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is selected.

[0148] In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0149] [ka] and R 15 are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , and -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0150] [ka] and n is 0. In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0151] [ka] where n is 0 and R 15 is C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, and -N(R 10 )(R 11In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0152] [ka] where n is 0 and R 15 is the unsubstituted C 1-6 Alkyl and C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0153] [ka] where n is 0 and R 15 is the unsubstituted C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 teeth

[0154] [ka] where n is 0 and R 15 Ha-CH 3 It is.

[0155] In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , -N(R10 )(R 11 ), -C(O)OR 10 , or -C(O)N(R 10 )(R 11 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen.

[0156] In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen, halogen, C1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 -OR 10 It is.

[0157] In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R3 is C 1-6 Alkyl or C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 -OR 10 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 -N(R 10 )(R 11 ).

[0158] In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR10 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 -OR 10 It is.

[0159] In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen or C 1-6In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 -OR 10 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 -N(R 10 )(R 11 ).

[0160] In some embodiments, a compound of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(R 9c In some embodiments, a compound of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(R9c )- and R 9c is hydrogen and C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(H)-. In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(R 9c )- and R 9c is C 1-6 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(R 9c )- and R 9c Ha-CH 3 In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -O-. In some embodiments, the compound is of formula (Ic'), (Ig'), (Ih'), (Ij'), (Ik'), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -S-.

[0161] In some embodiments, formula (I)

[0162] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, U is C, CH, or N; V is C, CH, or N; W is C(R 7a ), C(R 7a )(R 7b), O, S, N, or N(R 8a ) and X does not exist or C(R 7c ), C(R 7c )(R 7d ), O, S, N, or N(R 8b ) and Y does not exist or C(R 7e ), C(R 7e )(R 7f ), O, S, N, or N(R 8c ) and Z is C(R 7g ), C(R 7g )(R 7h ), O, S, N, or N(R 8d ) and L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 7b and R 7h combine to form a cycloalkyl or heterocycloalkyl ring; R 8a , R 8b , R 8c , and R 8d are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; or R 8a and R 7h are combined to form a heterocycloalkyl ring; or R 8d and R 7b are combined to form a heterocycloalkyl ring; R9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and R 13 are each independently 1-6 Alkyl, C2-6 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 is halogen, 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from

[0163] [ka] indicates a single or double bond such that all valences are satisfied.

[0164] In some embodiments, there are compounds of formula (I), or pharma- ceutically acceptable salts or solvates thereof, where U is C and V is C. In some embodiments, there are compounds of formula (I), or pharma- ceutically acceptable salts or solvates thereof, where U is N and V is C. In some embodiments, there are compounds of formula (I), or pharma- ceutically acceptable salts or solvates thereof, where U is C and V is N.

[0165] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y is C(R 7e In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, or C 1-6 Alkyl, and C 1-6 In some embodiments, the compound is of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, and C 1-6 In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, Y, and Z are C(H).

[0166] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7b In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c )(R 7d In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y is C(R 7e )(R 7f In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g )(R 7h In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, Y, and Z are C(H). 2 It is.

[0167] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7b In some embodiments, there are compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where X is absent. In some embodiments, there are compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where Y is C(R 7e )(R 7f In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g )(R 7h In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, Y, and Z are C(H). 2 It is.

[0168] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , or -C(O)N(R 10 )(R 11 In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 In some embodiments, the compound is of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen.

[0169] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 -OR 10 It is.

[0170] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 Alkyl, or C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 -OR 10 In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 -N(R 10 )(R 11 ).

[0171] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 -OR 10 It is.

[0172] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen, halogen, C1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen or C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 -OR 10 In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 -N(R 10 )(R 11 ).

[0173] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 2-9 heterocycloalkyl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 2-9 Heterocycloalkyl can have one, two, three, four, or five R 15Groups are optionally substituted.

[0174] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 2-9 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 is selected from piperidinyl, piperazinyl, and morpholinyl 2-9 Heterocycloalkyl, where piperidinyl, piperazinyl, and morpholinyl are each independently selected from one, two, three, four, or five R 15 In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, the compounds of formula (I) or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 and morpholinyl optionally substituted with a group.

[0175] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 3-8 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R6 1, 2, 3, 4, or 5 R 15 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 is cyclopropyl, optionally substituted with a group.

[0176] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 1-6 It is an alkyl.

[0177] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 6-10 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 is phenyl optionally substituted with a group.

[0178] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 1-9 It is heteroaryl.

[0179] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , and -N(R 10 )(R 11 In some embodiments, the compound is of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 each independently represents a halogen, an unsubstituted C 1-6 Alkyl and C 1-6 haloalkyl.

[0180] In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(R 9c In some embodiments, there are compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where L is -N(H)-. In some embodiments, there are compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where L is -O-. In some embodiments, there are compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where L is -S-. In some embodiments, there are compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where L is -C(O)-. In some embodiments, there are compounds of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, where L is -C(R 9a )(R 9bIn some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a is hydrogen, halogens, and C 1-6 In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9b is selected from hydrogen, halogen, and -OH. In some embodiments, there is a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -C(H). 2 -It is.

[0181] In some embodiments, the compound of formula (Ia)

[0182] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ), C(R 7a )(R 7b ), O, S, N, or N(R 8a ) and X does not exist or C(R 7c ), C(R 7c )(R 7d ), O, S, N, or N(R 8b ) and Y does not exist or C(R 7e ), C(R 7e )(R 7f ), O, S, N, or N(R 8c ) and Z is C(R 7g ), C(R 7g )(R 7h ), O, S, N, or N(R 8d ) and L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h are each independently hydrogen, halogen, -CN, or 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 7b and R 7h combine to form a cycloalkyl or heterocycloalkyl ring; R 8a , R 8b , R 8c , and R 8d are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; or R 8a and R 7h are combined to form a heterocycloalkyl ring; or R 8d and R 7b are combined to form a heterocycloalkyl ring; R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, 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, and 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, 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 is halogen, 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from

[0183] [ka] indicates a single or double bond such that all valences are satisfied.

[0184] In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y is C(R 7e In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, or C 1-6 Alkyl, and C 1-6In some embodiments, the compound is of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, and C 1-6 In some embodiments, there is a compound of Formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, Y, and Z are C(H).

[0185] In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7b In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c )(R 7d In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y is C(R 7e )(R 7f In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g )(R 7h In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, Y, and Z are C(H). 2 It is.

[0186] In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7b In some embodiments, there are compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, where X is absent. In some embodiments, there are compounds of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, where Y is C(R7e )(R 7f In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g )(R 7h In some embodiments, there is a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, Y, and Z are C(H). 2 It is.

[0187] In some embodiments, the compound of formula (Ib)

[0188] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ) or N, X is C(R 7c ) or N, Y is C(R 7e ) or N, Z is C(R 7g ) or N, L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6Alkenyl, 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 is halogen, 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, and 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, 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 is halogen, C1-6 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 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0189] In some embodiments, there is a compound of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a In some embodiments, there is a compound of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c In some embodiments, there is a compound of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y is C(R 7e In some embodiments, there is a compound of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g In some embodiments, there is a compound of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7gare each independently hydrogen, halogen, or C 1-6 Alkyl, and C 1-6 In some embodiments, the compound is of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, and C 1-6 In some embodiments, there is a compound of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, Y, and Z are C(H).

[0190] In some embodiments, the formula (Ic)

[0191] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R11 ), -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 R13 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and 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, 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 is halogen, 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 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0192] In some embodiments, the compound is of formula (Ic), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, or C 1-6 Alkyl, and C 1-6 In some embodiments, the compound is of formula (Ic), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g are each independently hydrogen, halogen, and C 1-6 In some embodiments, the compounds are of formula (Ic), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7e , and R 7g is hydrogen.

[0193] In some embodiments, the compound of formula (Id)

[0194] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a )(R 7b ), O, S, or N(R 8a ) and X does not exist or C(R 7c )(R 7d ), O, S, or N(R 8b ) and Y does not exist or C(R 7e ), (R 7f ), O, S, or N(R 8c ) and Z is C(R 7g )(R 7h ), O, S, N(R 8d ) and L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 7b and R 7h combine to form a cycloalkyl or heterocycloalkyl ring; R 8a , R 8b , R 8c , and R 8d are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; or R 8a and R 7h are combined to form a heterocycloalkyl ring; or R 8d and R 7b are combined to form a heterocycloalkyl ring; R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and R 13 are each independently1-6 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 is halogen, 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 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0195] In some embodiments, there is a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7bIn some embodiments, there is a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c )(R 7d In some embodiments, there is a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, wherein Y is C(R 7e )(R 7f In some embodiments, there is a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g )(R 7h In some embodiments, there is a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, Y, and Z are C(H). 2 It is.

[0196] In some embodiments, there is a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7b In some embodiments, there are compounds of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, where X is absent. In some embodiments, there are compounds of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, where Y is C(R 7e )(R 7f In some embodiments, there is a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g )(R 7h In some embodiments, there is a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, Y, and Z are C(H). 2 It is.

[0197] In some embodiments, the compound of formula (Ie)

[0198] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h are each independently hydrogen, halogen, -CN, or C 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 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 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 7b and R 7h combine to form a cycloalkyl or heterocycloalkyl ring; R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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 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, and 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, 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 is halogen, 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 14 and each R 15 are each independently halogen, -CN, 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, 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 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0199] In some embodiments, there is a compound of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h are each independently hydrogen, halogen, or C 1-6 Alkyl, and C 1-6 In some embodiments, the compound is of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h are each independently hydrogen, halogen, and C 1-6 In some embodiments, there is a compound of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g , and R 7h is hydrogen. In some embodiments, there is a compound of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , R 7e , R 7f , and R 7g is hydrogen, and R 7b and R7h are combined to form a cycloalkyl ring. In some embodiments, there is a compound of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , R 7e , R 7f , and R 7g is hydrogen, and R 7b and R 7h are combined to form a heterocycloalkyl ring.

[0200] In some embodiments, the formula (If)

[0201] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ), C(R 7a )(R 7b ), O, S, N, or N(R 8a ) and X does not exist or C(R 7c ), C(R 7c )(R 7d ), O, S, N, or N(R 8b ) and Z is C(R 7g ), C(R 7g )(R 7h ), O, S, N, or N(R 8d ) and L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, or C 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 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 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, -CN, 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 , -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(R12 )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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 8a , R 8b , and R 8d are each independently hydrogen, C 1-6Alkyl, and C 1-6 haloalkyl; or R 8a and R 7h are combined to form a heterocycloalkyl ring; or R 8d and R 7b are combined to form a heterocycloalkyl ring; R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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 C1-6 haloalkyl; R 12 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl, and 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, 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 is halogen, 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; Each R 14 and each R 15 are each independently halogen, -CN, 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 , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R11 ), -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from

[0202] [ka] indicates a single or double bond such that all valences are satisfied.

[0203] In some embodiments, the compound is of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a In some embodiments, there is a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c ) or N. In some embodiments, there is a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g )(R 7h ) or N(R 8d In some embodiments, there is a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7b ) or N(R 8a In some embodiments, there is a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c ) or N. In some embodiments, there is a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g ) or N.

[0204] In some embodiments, the compound is of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7b In some embodiments, there is a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein X is C(R 7c )(R 7d In some embodiments, there is a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g)(R 7h In some embodiments, there is a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof, wherein W, X, and Z are C(H). 2 It is.

[0205] In some embodiments, the formula (If)

[0206] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a )(R 7b ), O, S, or N(R 8a ) and X is C(R 7c ) or N, Z is C(R 7g ) or N, L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7b , R 7c , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 8a is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 10 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6Alkynyl, 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 is halogen, 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, and 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, 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 is halogen, 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 heteroaryl; and Each R 14 and each R 15 are each independently halogen, -CN, 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 , -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 2C(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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0207] In some embodiments, there is a compound of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is N(R 8a In some embodiments, there are compounds of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where W is O. In some embodiments, there are compounds of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where W is S. In some embodiments, there are compounds of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(R 7cIn some embodiments, there are compounds of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(H). In some embodiments, there are compounds of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where X is N. In some embodiments, there are compounds of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(R 7c In some embodiments, there are compounds of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(H). In some embodiments, there are compounds of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof, where Z is N.

[0208] In some embodiments, the compound of formula (Ih)

[0209] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ) or N, X is C(R 7c ) or N, Z is C(R 7g )(R 7h ), O, S, or N(R 8d ) and L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, or 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7c , R 7g , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 8d is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 9a and R 9bare each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, 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 is halogen, 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 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0210] In some embodiments, there is a compound of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is N(R 8dIn some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where Z is O. In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where Z is S. In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(R 7c In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(H). In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where X is N. In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where W is C(R 7a In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where W is C(H). In some embodiments, there are compounds of formula (Ih), or a pharma- ceutically acceptable salt or solvate thereof, where W is N.

[0211] In some embodiments, the compound of formula (Ii)

[0212] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a )(R 7b ), O, S, or N(R 8a ) and X does not exist or C(R 7c )(R 7d ), O, S, or N(R 8b ) and Z is C(R 7g )(R 7h ), O, S, N(R 8d ) and L is -C(R9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, -CN, or 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, 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 ), where 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 C1-9 Heteroaryl is halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 7b and R 7h combine to form a cycloalkyl or heterocycloalkyl ring; R 8a , R 8b , and R 8d are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; or R 8a and R 7h are combined to form a heterocycloalkyl ring; or R 8d and R 7b are combined to form a heterocycloalkyl ring; R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, wherein 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, 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, and 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, 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 is halogen, 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 14 and each R15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0213] In some embodiments, there is a compound of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a )(R 7b In some embodiments, there are compounds of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof, where W is O. In some embodiments, there are compounds of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(R 7c )(R 7d In some embodiments, there is a compound of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z is C(R 7g )(R 7h In some embodiments, there is a compound of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof, where Z is O. In some embodiments, there is a compound of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof, where W, X, and Z are C(H). 2 In some embodiments, there is a compound of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is O, Z is O, and X is C(F) 2 It is.

[0214] In some embodiments, the compound of formula (Ij)

[0215] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, -CN, 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 , -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) 2R 13 , and -CH 2 S(O) 2 N(R 10 )(R 11 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 7b and R 7h combine to form a cycloalkyl or heterocycloalkyl ring; R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, wherein 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, 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, and 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, 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 is halogen, 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 14 and each R 15are each independently halogen, -CN, 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 , -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), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0216] In some embodiments, there is a compound of formula (Ij), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, or C 1-6 Alkyl, and C 1-6 In some embodiments, the compound is of formula (Ij), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h are each independently hydrogen, halogen, and C 1-6 In some embodiments, there is a compound of formula (Ij), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7b , R 7c , R 7d , R 7g , and R 7h In some embodiments, there is a compound of formula (Ij), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , and R7g is hydrogen, and R 7b and R 7h are combined to form a cycloalkyl ring. In some embodiments, there is a compound of formula (Ij), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 7a , R 7c , R 7d , and R 7g is hydrogen, and R 7b and R 7h are combined to form a heterocycloalkyl ring.

[0217] In some embodiments, the formula (Ik)

[0218] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ) or N, X is C(R 7c )(R 7d ), O, S, or N(R 8b ) and Z is C(R 7g ) or N, L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently hydrogen, halogen, -CN, 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, -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 ), where 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, C 1-6 Alkyl, C1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7c , R 7d , and R 7g are each independently hydrogen, halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 8b is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; R 9a and R 9bare each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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, and R 13 are each independently 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, 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 is halogen, 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 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0219] In some embodiments, there is a compound of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a). In some embodiments, there are compounds of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where W is C(H). In some embodiments, there are compounds of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where W is N. In some embodiments, there are compounds of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where X is S or O. In some embodiments, there are compounds of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where X is S. In some embodiments, there are compounds of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where X is O. In some embodiments, there are compounds of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(R 7g In some embodiments, there are compounds of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(H). In some embodiments, there are compounds of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof, where Z is N.

[0220] In some embodiments, the formula (Im)

[0221] [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, W is C(R 7a ) or N, X is C(R 7c ) or N, Z is C(R 7g ) or N, L is -C(R 9a )(R 9b )-, -C(O)-, -O-, -S-, or -N(R 9c )-and R 1 , R 2 , R 3 , R4 , and R 5 are each independently hydrogen, halogen, -CN, 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 , -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(R10 )(R 11 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 1 and R 2 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 2 and R 3 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 3 and R 4are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 optionally substituted with a group, or R 4 and R 5 are combined to form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, the 4-, 5-, or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, or the phenyl ring is optionally joined to one, two, or three R 14 is optionally substituted with a group; R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is one, two, three, four, or five R 15 is optionally substituted with a group; R 7a , R 7c , and R 7g are each independently hydrogen, halogen, -CN, 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, -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 ), where 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, C 1-6 Alkyl, C1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 Optionally substituted with one, two, or three groups selected from R 9a and R 9b are each independently hydrogen, halogen, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 alkoxy; R 9c is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; 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, 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 is halogen, 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 12are each independently hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl, and 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, 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 is halogen, 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 14 and each R 15 are each independently halogen, -CN, 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 , -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 ), where 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, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , and -N(R 10 )(R 11 ) is optionally substituted with one, two, or three groups selected from

[0222] In some embodiments, there is a compound of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein W is C(R 7a In some embodiments, there are compounds of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, where W is C(H). In some embodiments, there are compounds of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, where W is N. In some embodiments, there are compounds of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(R 7c In some embodiments, there are compounds of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, where X is C(H). In some embodiments, there are compounds of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, where X is N. In some embodiments, there are compounds of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(R 7g In some embodiments, there are compounds of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, where Z is C(H). In some embodiments, there are compounds of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof, where Z is N.

[0223] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , -N(R 10 )(R 11 ), -C(O)OR 10 , or -C(O)N(R 10 )(R 11In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is C 1-6 In some embodiments, the compound is of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen.

[0224] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 is C 1-6 In some embodiments that are haloalkyl, there is a compound of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 2 -OR 10 It is.

[0225] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 Alkyl or C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 -OR 10 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 3 -N(R 10 )(R 11 ).

[0226] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or -OR 10 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is C 1-6In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 is C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 4 -OR 10 It is.

[0227] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 10 , or -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen or C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is C1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 is C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 -OR 10 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 5 -N(R 10 )(R 11 ).

[0228] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 is C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 2-9 heterocycloalkyl, wherein C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 2-9 Heterocycloalkyl can have one, two, three, four, or five R 15 Groups are optionally substituted.

[0229] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 2-9 In some embodiments, the compounds are of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 is selected from piperidinyl, piperazinyl, and morpholinyl 2-9 Heterocycloalkyl, where piperidinyl, piperazinyl, and morpholinyl are each independently selected from one, two, three, four, or five R 15 In some embodiments, the compounds are of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, the compounds are of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, the compounds are of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R15 and morpholinyl optionally substituted with a group.

[0230] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 3-8 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, the compounds are of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, the compounds are of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 In some embodiments, the compounds are of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15is cyclopropyl, optionally substituted with a group.

[0231] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 1-6 It is an alkyl.

[0232] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 6-10 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 is phenyl optionally substituted with a group.

[0233] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 6 1, 2, 3, 4, or 5 R 15 C optionally substituted with a group 1-9 It is heteroaryl.

[0234] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 are each independently a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -OR 10 , and -N(R 10 )(R 11 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 15 are each independently a halogen, an unsubstituted C 1-6 Alkyl, and C 1-6 Selected from haloalkyl

[0235] In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(R 9c)-. In some embodiments, there is a compound of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -N(H)-. In some embodiments, there is a compound of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -O-. In some embodiments, there is a compound of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -S-. In some embodiments, there is a compound of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -C(O)-. In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -C(R 9a )(R 9b In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9a is hydrogen, halogens, and C 1-6 In some embodiments, the compound is of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein R 9bis selected from hydrogen, halogen, and -OH. In some embodiments, there is a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), or (Im), or a pharma- ceutically acceptable salt or solvate thereof, wherein L is -C(H). 2 -It is.

[0236] In some embodiments,

[0237] [ka]

[0238] [ka] Provided herein is a compound selected from:

[0239] Any combination of the above groups for the various variables is contemplated herein. Throughout the specification, groups and substituents thereof can be selected by one of ordinary skill in the art to provide stable moieties and compounds.

[0240] In some embodiments, a therapeutic agent (e.g., a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im')) is present in the pharmaceutical composition as a pharma- ceutically acceptable salt. In some embodiments, the compounds described above are suitable for any of the methods or compositions described herein.

[0241] Further forms of the compounds disclosed herein Isomers Furthermore, in some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein have one or more double bonds. The compounds provided herein include all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers and their corresponding mixtures. In some circumstances, the compounds exist as tautomers. The compounds described herein include all tautomers possible within the formulas described herein. In some circumstances, the compounds described herein have one or more chiral centers, each of which exists in the R or S configuration. The compounds described herein include all diastereomeric, enantiomeric, and epimeric forms, as well as their corresponding mixtures. In further embodiments of the compounds and methods provided herein, mixtures of enantiomers and / or diastereoisomers derived from a single preparative step, combination, or interconversion are useful for the applications described herein. In some embodiments, the compounds described herein are prepared as optically pure enantiomers by chiral chromatographic separation of a racemic mixture. In some embodiments, the compounds described herein are prepared as individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers, and recovering the optically pure enantiomers. In some embodiments, dissociable complexes are preferred (e.g., crystalline diastereomeric salts). In some embodiments, diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and are separated by taking advantage of these dissimilarities. In some embodiments, diastereomers are separated by chiral chromatography, or preferably, separation / resolution techniques based on differences in solubility.In some embodiments, the optically pure enantiomer is recovered, along with the resolving agent, by any practical means that does not result in racemization.

[0242] labeled compound In some embodiments, the compounds described herein are present in their isotopically labeled form. In some embodiments, the methods disclosed herein include methods of treating disease by administering such isotopically labeled compounds. In some embodiments, the methods disclosed herein include methods of treating disease by administering such isotopically labeled compounds as pharmaceutical compositions. Thus, in some embodiments, the compounds disclosed herein include isotopically labeled compounds, which are identical to the compounds listed herein, but for the fact that one or more atoms are replaced with atoms having atomic masses or mass numbers different from the atomic masses or mass numbers normally found in nature. Examples of isotopes incorporated into the compounds described herein are each: 2 H, 3 H, 13 C. 14 C. 15 N, 17 O. 18 O. 31 P, 32 P, 35 S, 18 F, and 36 The isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chloride, such as Cl, are included. Compounds described herein, and pharma- ceutically acceptable salts, esters, solvates, hydrates, or derivatives thereof, that contain the aforementioned isotopes and / or other isotopes of other atoms, are within the scope of the present invention. Certain isotopically labeled compounds, e.g., 3 H and 14 Compounds that incorporate a radioactive isotope, such as C, are useful in drug and / or substrate tissue distribution assays. 3 H) and carbon 14-14 (i.e. 14 C) isotopes are particularly preferred for their ease of preparation and detectability. Additionally, deuterium (i.e.,2 Substitution with heavy isotopes, such as H, offers certain therapeutic advantages due to increased metabolic stability, for example increased in vivo half-life or reduced dosage requirements. In some embodiments, isotopically labeled compounds, pharma- ceutically acceptable salts, esters, solvates, hydrates, or derivatives thereof are prepared by any suitable method.

[0243] In some embodiments, the compounds described herein are labeled by other means, including but not limited to, a chromophore or fluorescent moiety, a bioluminescent label, or a chemiluminescent label.

[0244] Pharmaceutically acceptable salts In some embodiments, the compounds described herein are present as their pharma- ceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharma- ceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharma- ceutically acceptable salts as pharmaceutical compositions.

[0245] In some embodiments, the compounds described herein have acidic or basic groups and thus react with any of a number of inorganic or organic bases, as well as inorganic and organic acids, to form pharma- ceutically acceptable salts. In some embodiments, these salts are prepared during the final isolation and purification of the compounds disclosed herein, or in situ by separately reacting the purified compounds in free form with an appropriate acid or base and isolating the salt thus formed.

[0246] solvate In some embodiments, the compounds described herein exist as solvates. In some embodiments, there are methods of treating diseases by administering such solvates. Further described herein are methods of treating diseases by administering such solvates as pharmaceutical compositions.

[0247] Solvates contain stoichiometric or non-stoichiometric amounts of solvent, and in some embodiments, are formed during the process of crystallization with pharma- ceutically acceptable solvents such as water, ethanol, etc. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of the compounds described herein are suitably prepared or formed during the process described herein. By way of example only, hydrates of the compounds described herein are suitably prepared by recrystallization from aqueous / organic solvent mixtures, using organic solvents including, but not limited to, dioxane, tetrahydrofuran, or MeOH. Furthermore, the compounds provided herein exist in unsolvated forms as well as solvated forms. In general, solvated forms are considered equivalent to unsolvated forms for the purposes of the compounds and methods provided herein.

[0248] Compound synthesis In some embodiments, the synthesis of the compounds described herein is accomplished using means described in the chemical literature, using methods described herein, or by a combination thereof. In addition, solvents, temperatures, and other reaction conditions indicated herein may be varied.

[0249] In other embodiments, the starting materials and reagents used in the synthesis of the compounds described herein are synthesized or obtained from commercial sources, such as, but not limited to, Sigma-Aldrich, Fischer Scientific (Fischer Chemicals), and AcrosOrganics.

[0250] In further embodiments, the compounds described herein, and other related compounds having various substituents, can be prepared by any method, technique, or method known in the art, including, but not limited to, the synthesis and preparation of compounds of the present invention, using techniques and materials described herein, and other methods and techniques known in the art, such as those described in, for example, Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989), March, Advanced Organic Chemistry 4th Ed., (Wiley 1992); Carey and Sundberg, Advanced Organic Chemistry 4th Ed., Vols. A and B (Plenum 2000, 2001), and Green and Wuts, Protective Groups in Organic Synthesis 3rd Ed. Ed., (Wiley 1999) (all of which are incorporated by reference for the purposes of this disclosure). General methods for the preparation of compounds as disclosed herein may be derived from reactions, which may be modified using appropriate reagents and conditions to introduce the various moieties found in the formulae as provided herein. The following synthetic methods may be utilized as a guide.

[0251] Use of Protecting Groups In the reactions described, it may be necessary to protect reactive functional groups (e.g., hydroxy, amino, imino, thio, or carboxy groups) if desired in the final product to avoid their undesired participation in the reaction. Protecting groups are used to block some or all of the reactive moieties and to prevent such groups from participating in chemical reactions until the protecting group is removed. It is preferred that each protecting group is removable by a different means. Protecting groups that are cleaved under completely different reaction conditions fulfill the requirement of differential removal.

[0252] Protecting groups can be removed by acid, base, reducing conditions (e.g., hydrogenolysis), and / or oxidative conditions. Groups such as trityl, dimethoxytrityl, acetal, and t-butyldimethylsilyl are acid labile and may be used to protect carboxy and hydroxy reactive moieties in the presence of amino groups protected with Cbz groups (removable by hydrogenolysis) and Fmoc groups (base labile). Carboxylic acid and hydroxy reactive moieties can be blocked with base labile groups such as, but not limited to, methyl, ethyl, and acetyl in the presence of amines blocked with acid labile groups such as t-butyl carbamate, or carbamates that are both acid and base stable but removable by hydrolysis.

[0253] Carboxylic acid and hydroxy reactive sites may also be blocked with hydrolytically removable protecting groups such as benzyl groups, while amine groups capable of hydrogen bonding with acids may be blocked with base-labile groups such as Fmoc. Carboxylic acid reactive sites may be protected by conversion to simple ester compounds as exemplified herein, including conversion to alkyl esters, or may be blocked with oxidatively removable protecting groups such as 2,4-dimethoxybenzyl, while coexisting amino groups may be blocked with fluoride-labile silyl carbamates.

[0254] Allyl blocking groups are useful in the presence of acid and base protecting groups because the former are stable and can be subsequently removed by metal or pi-acid catalysts. For example, an allyl-blocked carboxylic acid can be deprotected with a Pd0 catalyzed reaction in the presence of acid-labile t-butyl carbamate or base-labile acetate amine protecting groups. However, another form of protecting group is a resin to which a compound or intermediate can be attached. As long as the residue is attached to the resin, its functional group is blocked and therefore cannot react. Once released from the resin, the functional group is available for reaction.

[0255] Typically, the blocking / protecting group may be selected from:

[0256] [ka]

[0257] Detailed descriptions of other protecting groups and techniques applicable to the creation and removal of protecting groups are described in Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, NY, 1999, and Kocienski, Protective Groups, Thieme Verlag, New York, NY, 1994, which are incorporated herein by reference for their disclosure.

[0258] Treatment and prevention methods In some embodiments, there is a method of treating a metabolic disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a method of treating a metabolic disease in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the metabolic disease is selected from type 2 diabetes, atherosclerosis, obesity, and gout. In some embodiments, there is a method of treating type 2 diabetes in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a method of treating atherosclerosis in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof.In some embodiments, there is a method of treating obesity in a patient in need of treatment, comprising the step of administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a method of treating gout in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof.

[0259] In some embodiments, there is a method of treating liver disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a method of treating liver disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the liver disease is selected from nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), viral hepatitis, or cirrhosis.

[0260] In some embodiments, there is a method of treating a pulmonary disease in a patient in need of treatment, comprising the step of administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the pulmonary disease is selected from asthma, COPD, and idiopathic pulmonary fibrosis.

[0261] In some embodiments, there is a method of treating a central nervous system disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the central nervous system disease is selected from Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease. In some embodiments, there is a method of treating a central nervous system disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the central nervous system disease is selected from Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, traumatic brain injury, ischemic stroke and reperfusion, hemorrhagic stroke, epilepsy, and depression.

[0262] In some embodiments, there is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the disease is rheumatoid arthritis. In some embodiments, there is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof; and wherein the disease is multiple sclerosis. In certain embodiments, there is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the disease is psoriasis.In some embodiments, there is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the disease is lupus. In some embodiments, there is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the disease is inflammatory bowel disease. In some embodiments, there is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the disease is Crohn's disease. In some embodiments, there is a method of treating an inflammatory or autoimmune disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the disease is ulcerative colitis.

[0263] In some embodiments, there is a method of treating cardiovascular disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a method of treating a cardiovascular disease in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof, wherein the cardiovascular disease is atherosclerosis or stroke. In some embodiments, there is a method of treating atherosclerosis in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a method of treating stroke in a patient in need of treatment, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof.

[0264] Pharmaceutical Compositions and Methods of Administration The NLRP3 inhibitors described herein are administered to subjects in a biologically compatible form suitable for administration to treat or prevent disease, disorder, or illness. The administration of the NLRP3 inhibitors as described herein can be in any pharmacological form, including a therapeutically effective amount of the NLRP3 inhibitor alone or in combination with a pharmacologic acceptable carrier.

[0265] In certain embodiments, the compounds described herein are administered as pure chemicals.In other embodiments, the compounds described herein are combined with pharma- ceutically suitable or acceptable carriers (also referred to herein as pharma- ceutically suitable (or acceptable) excipients, physiologically suitable (or acceptable) excipients, or physiologically suitable (or acceptable) carriers) that are selected based on selected route of administration and standard pharmaceutical practice, for example, as described in Remington: The Science and Practice of Pharmacy (Gennaro, 21st Ed. Mack Pub. Co., Easton, PA (2005)).

[0266] Thus, provided herein are pharmaceutical compositions comprising at least one compound described herein, or a pharma- ceutically acceptable salt thereof, together with one or more pharma- ceutically acceptable carriers. A carrier (or excipient) is acceptable or suitable if it is compatible with the other ingredients of the composition and not deleterious to the recipient (i.e., subject) of the composition.

[0267] In some embodiments, there is a pharmaceutical composition comprising a pharma- ceutically acceptable carrier and a compound of formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is provided a pharmaceutical composition comprising a pharma- ceutically acceptable carrier and a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is provided a pharmaceutical composition comprising a pharma- ceutically acceptable carrier and a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof.

[0268] Another embodiment provides a pharmaceutical composition consisting essentially of a pharma- ceutically acceptable carrier and a compound of formula (I), (Ia), (Ib), (Ic), (Ic'), (Id), (Ie), (If), (Ig), (Ig'), (Ih), (Ih'), (Ii), (Ij), (Ij'), (Ik), (Ik'), (Im), or (Im'), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition consisting essentially of a pharma- ceutically acceptable carrier and a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition consisting essentially of a pharma- ceutically acceptable carrier and a compound of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition consisting essentially of a pharma- ceutically acceptable carrier and a compound of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutically acceptable carrier and a compound of formula (Ic), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutically acceptable carrier and a compound of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutically acceptable carrier and a compound of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutically acceptable carrier and a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutical carrier and a compound of formula (Ig), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutical carrier and a compound of formula (Ih), or a pharma- ceutical acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition consisting essentially of a pharma- ceutically acceptable carrier and a compound of formula (Ii), or a pharma- ceutically acceptable salt or solvate thereof.In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutically acceptable carrier and a compound of formula (Ij), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutically acceptable carrier and a compound of formula (Ik), or a pharma- ceutically acceptable salt or solvate thereof. In some embodiments, there is a pharmaceutical composition that consists essentially of a pharma- ceutically acceptable carrier and a compound of formula (Im), or a pharma- ceutically acceptable salt or solvate thereof.

[0269] In certain embodiments, the compounds described herein are substantially pure, in that they contain less than about 5%, or less than about 1%, or less than about 0.1%, of other small organic molecules, e.g., contaminating intermediates or by-products produced during one or more of the steps of a synthetic process.

[0270] These formulations include those suitable for oral, topical, buccal, parenteral (eg, subcutaneous, intramuscular, intradermal, or intravenous) or aerosol administration.

[0271] Typical pharmaceutical compositions are used in the form of pharmaceutical preparations, e.g., solid, semi-solid, or liquid, which contain one or more of the disclosed compounds as active ingredients in a mixture with organic or inorganic carriers or excipients suitable for external, enteral, or parenteral use. In some embodiments, the active ingredients are compounded with a typically non-toxic, pharma- ceutically acceptable carrier, e.g., tablets, pellets, capsules, suppositories, solutions, emulsions, suspensions, and other forms suitable for use. The active subject compound is included in the pharmaceutical composition in an amount sufficient to exert the desired effect on the disease process or condition.

[0272] In some embodiments, the NLRP3 inhibitors described herein are administered to a subject in a biologically compatible form suitable for topical administration to treat or prevent a skin disease, disorder, or condition. "Biologically compatible form suitable for topical administration" refers to a form of the NLRP3 inhibitor administered such that any toxic effects outweigh the therapeutic effect of the inhibitor. The administration of the NLRP3 inhibitors as described herein can be in any pharmacological form, including a therapeutically effective amount of the NLRP3 inhibitor alone or in combination with a pharma- ceutically acceptable carrier.

[0273] The topical administration of NLRP3 inhibitors can be presented in the form of aerosol, semi-solid pharmaceutical composition, powder, or solution. The term "semi-solid composition" refers to ointments, creams, salves, jellies, or other pharmaceutical compositions with substantially similar consistency suitable for application to the skin. Examples of semi-solid compositions are shown in Chapter 17 of The Theory and Practice of Industrial Pharmacy, Lachman, Lieberman and Kanig, published by Lea and Febiger (1970), and Chapter 67 of Remington's Pharmaceutical Sciences, 15th Edition (1975) published by Mack Publishing Company.

[0274] Skin or skin patches are another method for transdermally delivering the therapeutic or pharmaceutical compositions described herein. Patches can provide absorption enhancers, such as DMSO, to increase absorption of the compound. Patches can include those that control the rate of drug delivery to the skin. Patches can provide a variety of administration systems, including reservoir systems or monolithic systems, respectively. Reservoir designs may have, for example, four layers: an adhesive layer that directly contacts the skin, a control membrane that controls the diffusion of the drug molecules, a reservoir of drug molecules, and a water-resistant backing. Such designs deliver a uniform amount of drug over a specified time, so the delivery rate must be less than the saturation limit of different types of skin. For example, monolithic designs usually have only three layers: an adhesive layer, a polymer matrix containing the compound, and a water-resistant backing. This design brings a saturating amount of drug to the skin. With this design, the delivery is controlled by the skin. If the amount of drug in the patch decreases below the saturation level, the delivery rate will decrease.

[0275] In one embodiment, the topical composition may take the form of an ointment, e.g. with polyethylene glycol (PEG) as carrier, such as the standard ointment DAB8 (50% PEG 300, 50% PEG 1500), or as an emulsion, in particular a microemulsion based on water-in-oil or oil-in-water, optionally with the addition of liposomes, e.g. a hydrogel based on polyacrylic acid or polyacrylamide. Suitable permeation enhancers (entraining agents) include sulfoxide derivatives such as dimethyl sulfoxide (DMSO) or decyl methyl sulfoxide (decyl-MSO) and transcutol (diethylene glycol monoethyl ether) or cyclodextrins, as well as pyrrolidones such as 2-pyrrolidone, N-methyl-2-pyrrolidone, 2-pyrrolidone-5-carboxylic acid, or biodegradable N-(2-hydroxyethyl)-2-pyrrolidone and its fatty acid esters, urea derivatives such as dodecylurea, 1,3-didodecylurea, and 1,3-diphenylurea, and terpenes such as D-limonene, menthone, a-terpinol, carbol, limonene oxide, or 1,8-cineole.

[0276] Ointments, pastes, creams, and gels can contain excipients such as starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, and talc, or mixtures thereof. Powders and sprays can contain excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicate, and polyamide powder, or mixtures of these substances. Solutions of nanocrystalline antimicrobial metals can be converted into aerosols or sprays by any of the known means routinely used for the manufacture of aerosol pharmaceuticals. In general, such methods involve pressurizing, or providing a means for pressurizing, a container of the solution, usually with an inert carrier gas, and passing the pressurized gas through a small orifice. Sprays can further contain conventional propellants such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons such as butane and propane.

[0277] The carrier may also contain other pharma- ceutically acceptable excipients to modify or maintain the pH, osmolality, viscosity, clarity, color, sterility, stability, dissolution rate, or odor of the formulation. Anti-skin aging compositions may also further include antioxidants, sunscreens, natural retinoids (e.g., retinol), and other additives commonly found in skin treatment compositions.

[0278] In some embodiments for preparing solid compositions such as tablets, the primary active ingredient is mixed with a pharmaceutical carrier, such as conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate, or gums, and other pharmaceutical diluents, such as water, to form a solid preformulation composition containing a homogenous mixture of the disclosed compound or a non-toxic pharma- ceutically acceptable salt thereof. When such a preformulation composition is referred to as homogenous, it is meant that the active ingredient is evenly dispersed throughout the composition such that the composition may be readily subdivided into equally effective unit dosage forms, such as tablets, pills, and capsules.

[0279] In solid dosage forms for oral administration (capsules, tablets, pills, dragees, powders, granules, etc.), the subject compositions may be administered in the form of a solid dosage form containing one or more pharma- ceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and / or one or more of the following: (1) fillers or extenders, such as starch, cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, lactose, sucrose, glucose, mannitol, and / or silicic acid; (2) carboxymethylcellulose, hypromellose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and / or alginates; The composition may be mixed with any of the following: (1) a binder such as cassia, (2) a humectant such as glycerin, (3) a humectant such as glycerin, (4) a disintegrant such as crospovidone, croscarmellose sodium, sodium starch glycolate, agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (5) a solution retardant such as paraffin, (6) an absorption promoter such as a quaternary ammonium compound, (7) a humectant such as docusate sodium, cetyl alcohol, and glycerol monostearate, (8) an absorbent such as kaolin and bentonite clay, (9) a lubricant such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof, and (10) a coloring agent. In the case of capsules, tablets, and pills, in some embodiments, the composition includes a buffering agent. In some embodiments, solid compositions of a similar type are also employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like.

[0280] In some embodiments, tablets are made by compression or molding, optionally with one or more accessory ingredients. In some embodiments, compressed tablets are prepared using binders (e.g., gelatin or hydroxypropylmethylcellulose), lubricants, inert diluents, preservatives, disintegrants (e.g., sodium starch glycolate or cross-linked sodium carboxymethylcellulose), surface active agents, or dispersants. In some embodiments, molded tablets are made by molding in a suitable machine a mixture of the subject composition moistened with an inert liquid diluent. In some embodiments, tablets, as well as other solid dosage forms such as dragees, capsules, pills, and granules, are scored or prepared with coatings and shells, such as enteric coatings and other coatings.

[0281] Compositions for inhalation or insufflation include solutions and suspensions in pharma- ceutically acceptable aqueous or organic solvents, or mixtures thereof, and powders. Liquid dosage forms for oral administration include pharma-ceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the subject compositions, in some embodiments, liquid dosage forms include inert dilu...

Claims

**Claim 1** A compound having the structure of formula (Im), or a pharmaceutically acceptable salt or solvate thereof, wherein: 【Chemical 1】 W is C(R7a) or N; X is C(R7c) or N; Z is C(R7g) or N; L is -C(R9a)(R9b)-, -C(O)-, -O-, -S-, or -N(R9c)-; R6 is selected from C1-6 alkyl, C3-8 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, wherein C1-6 alkyl, C3-8 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with one, two, three, four, or five R15 groups; ​ R1, R2, R3, R4, and R5 are each independently selected from hydrogen, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, C1-9 heteroaryl, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), -C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, S(=O)(=NH)N(R10)(R11), -CH2C(O)N(R10)(R11), -CH2N(R12)C(O)R13, -CH2S(O)2R13, and -CH2S(O)2N(R10)(R11), where C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, -OR10, and -N(R10)(R11), or R1 and R2 are combined to form a 4-membered, 5-membered, or 6-membered cycloalkyl ring, a 4-membered, 5-membered, or 6-membered heterocycloalkyl ring, a 5-membered or 6-membered heteroaryl ring, or a phenyl ring, and the 4-membered, 5-membered, or 6-membered cycloalkyl ring, the 4-membered, 5-membered, or 6-membered heterocycloalkyl ring, the 5-membered or 6-membered heteroaryl ring, or the phenyl ring is optionally substituted with one, two, or three R14 groups, or R2 and R3When combined, they form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, 4-, 5-, or 6-membered heterocycloalkyl ring, 5- or 6-membered heteroaryl ring, or phenyl ring is optionally substituted with one, two, or three R14 groups, or R3 and R4, when combined, form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, 4-, 5-, or 6-membered heterocycloalkyl ring, 5- or 6-membered heteroaryl ring, or phenyl ring is optionally substituted with one, two, or three R14 groups, or R4 and R5, when combined, form a 4-, 5-, or 6-membered cycloalkyl ring, a 4-, 5-, or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a phenyl ring, and the 4-, 5-, or 6-membered cycloalkyl ring, 4-, 5-, or 6-membered heterocycloalkyl ring, 5- or 6-membered heteroaryl ring, or phenyl ring is optionally substituted with one, two, or three R14 groups. ​ R7a, R7c, and R7g are each independently selected from hydrogen, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, C1-9 heteroaryl, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), -C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, S(=O)(=NH)N(R10)(R11), -CH2C(O)N(R10)(R11), -CH2N(R12)C(O)R13, -CH2S(O)2R13, and -CH2S(O)2N(R10)(R11), where C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, -OR10, and -N(R10)(R11). R9a and R9b are each independently selected from hydrogen, halogen, -OH, C1-6 alkyl, C1-6 haloalkyl, and C1-6 alkoxy. R9c is selected from hydrogen, C1-6 alkyl, and C1-6 haloalkyl. Each R10 is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, Each R11 is independently selected from hydrogen, C1-6 alkyl, and C1-6 haloalkyl, Each R12 is independently selected from hydrogen, C1-6 alkyl, and C1-6 haloalkyl, and Each R13 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, Each R14 and each R15 are each independently selected from halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, C1-9 heteroaryl, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), -C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, S(=O)(=NH)N(R10)(R11), -CH2C(O)N(R10)(R11), -CH2N(R12)C(O)R13, -CH2S(O)2R13, and -CH2S(O)2N(R10)(R11), wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, -OR10, and -N(R10)(R11), a compound, or a pharmaceutically acceptable salt or solvate thereof.

2. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein W, X, and Z are C(H). **Claim 3** The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, or -OH; R2 is hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, or -OR10; R3 is hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, -OR10, or -N(R10)(R11); R4 is hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, or -OR10; and R5 is hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, -OR10, or -N(R10)(R11). **Claim 4** The compound according to claim 3, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is -OH. **Claim 5** The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R2 is hydrogen and R4 is hydrogen. **Claim 6** The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R3 is C1-6 alkyl or C1-6 haloalkyl. **Claim 7** The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R5 is hydrogen or C1-6 alkyl. **Claim 8** The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R6 is C2-9 heterocycloalkyl optionally substituted with one, two, three, four, or five R15 groups. **Claim 9** The compound according to claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein R6 is piperidinyl optionally substituted with one, two, three, four, or five R15 groups. **Claim 10** The compound according to claim 9, or a pharmaceutically acceptable salt or solvate thereof, wherein each R15 is independently selected from halogen, unsubstituted C1-6 alkyl, and C1-6 haloalkyl. **Claim 11** The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein L is -N(H)-.

12. 【Fig. 2】 The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, selected from...

13. A pharmaceutical composition comprising the compound according to any one of Claims 1 to 12, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

14. Use of the compound according to any one of Claims 1 to 12, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a metabolic disorder in a patient in need of treatment for a metabolic disorder.

15. The metabolic disorder is selected from type 2 diabetes, atherosclerosis, obesity, and gout; the liver disease is selected from non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), viral hepatitis, and cirrhosis; the lung disease is selected from asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis; the central nervous system disease is selected from Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, traumatic brain injury, ischemic stroke and reperfusion, hemorrhagic stroke, epilepsy, and depression; the cardiovascular disease is atherosclerosis or stroke; and the inflammatory or autoimmune disease is selected from rheumatoid arthritis, multiple sclerosis, psoriasis, lupus, inflammatory bowel disease, Crohn's disease, and ulcerative colitis. The use according to Claim 14.

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