WO2023088233A1 - Lysine acetyltransferase 6a (kat6a) inhibitors and uses thereof - Google Patents

Lysine acetyltransferase 6a (kat6a) inhibitors and uses thereof Download PDF

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WO2023088233A1
WO2023088233A1 PCT/CN2022/131893 CN2022131893W WO2023088233A1 WO 2023088233 A1 WO2023088233 A1 WO 2023088233A1 CN 2022131893 W CN2022131893 W CN 2022131893W WO 2023088233 A1 WO2023088233 A1 WO 2023088233A1
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alkyl
heteroaryl
heterocycloalkyl
cycloalkyl
aryl
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English (en)
French (fr)
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Xin Cheng
Luoheng QIN
Feng Ren
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InSilico Medicine IP Ltd
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InSilico Medicine IP Ltd
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Priority to PE2024001081A priority Critical patent/PE20241355A1/es
Priority to KR1020247019546A priority patent/KR20240109267A/ko
Priority to CN202280089104.7A priority patent/CN118556053A/zh
Priority to EP22894767.7A priority patent/EP4433474A4/en
Priority to JP2024529158A priority patent/JP2024543512A/ja
Priority to IL312696A priority patent/IL312696A/en
Priority to CA3237830A priority patent/CA3237830A1/en
Priority to MX2024005839A priority patent/MX2024005839A/es
Priority to AU2022390319A priority patent/AU2022390319A1/en
Application filed by InSilico Medicine IP Ltd filed Critical InSilico Medicine IP Ltd
Publication of WO2023088233A1 publication Critical patent/WO2023088233A1/en
Priority to US18/486,369 priority patent/US20240109880A1/en
Priority to US18/507,566 priority patent/US12091406B2/en
Priority to CL2024001466A priority patent/CL2024001466A1/es
Anticipated expiration legal-status Critical
Priority to CONC2024/0007129A priority patent/CO2024007129A2/es
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • Lysine acetyltransferase 6A belongs to the MYST family of acetyltransferases and was first discovered approximately 25 years ago. KAT6A controls fundamental cellular processes, including gene transcription, cellular senescence, cardiac septum development, memory T-cell diversity, and maintenance of normal hematopoietic stem cells. Dysregulation of KAT6A acetyltransferase activity or aberrant expression of KAT6A has been associated with oncogenic function in a number of cancers, including leukemia, glioma, endometrial serous carcinoma, and breast cancer. As such, compounds that inhibit KAT6A are potential agents for treating a variety of cancers.
  • Y 1 is CR 1a or N
  • Y 2 is CR 2a or N
  • Y 3 is CR 3a or N
  • Y 4 is CR 4a or N
  • Y 5 is CR 5a or N
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N; wherein at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N;
  • X is selected from -C (R 6 ) (R 6a ) -, -O-, and -N (R 7 ) -;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R
  • R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1- 9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (
  • provided herein is a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof
  • Y 1 is CR 1a or N
  • Y 2 is CR 2a or N
  • Y 3 is CR 3a or N
  • Y 4 is CR 4a or N
  • Y 5 is CR 5a or N
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N
  • X is -O-or -S-;
  • X is selected from -C (R 6 ) (R 6a ) -and -N (R 7 ) -, and wherein at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (
  • provided herein is a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof,
  • Y 1 is CR 1a or N
  • Y 2 is CR 2a or N
  • Y 3 is CR 3a or N
  • Y 4 is CR 4a or N
  • Y 5 is CR 5a or N
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N
  • X is -O-
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 1a and R 5a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1a and R 5a are independently selected from hydrogen and -OR 10 .
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 1a and R 5a are -OR 10 .
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 is C 1-6 alkyl.
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 is -CH 3 .
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein Y 2 is N;Y 3 is CR 3a ; and Y 4 is CR 4a .
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein Y 2 is N; Y 3 is CR 3a ; and Y 4 is N.
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein Z 1 is CR 1b ; Z 2 is N; and Z 3 is CR 3b .
  • a compound of Formula (I) , (I’) , or (Ia) or a pharmaceutically acceptable salt or solvate thereof, wherein R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • provided herein is a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, and C 1-6 alkyl.
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are hydrogen.
  • X is selected from -C (R 6 ) (R 6a ) -, -O-, and -N (R 7 ) -;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1- 9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • R 8a , R 8b , R 8c , R 8d , R 8e , R 9b , and R 9c are each independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 ,
  • R 9a is selected from C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 14 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C (O) N
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • R 14 is independently selected from hydrogen, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 2-6 alkenyl, C 2-6 alkynyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a , each R 15b , each R 15c , each R 15d , and each R 15e are each independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) ,
  • provided herein is a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 9b is selected from hydrogen, halogen, and C 1-6 alkyl.
  • R 9b is hydrogen.
  • provided herein is a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 9a is -OR 14 .
  • provided herein is a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 14 is C 1-6 haloalkyl.
  • a compound of Formula (II) or a pharmaceutically acceptable salt or solvate thereof, wherein R 9a and R 9b are combined to form a C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, or C 2-9 heteroaryl, wherein C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, and C 2-9 heteroaryl are optionally substituted with one, two, or three groups selected from R 15e .
  • provided herein is a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 9a and R 9b are combined to form a C 2-9 heterocycloalkyl optionally substituted with one, two, or three groups selected from R 15e .
  • a compound of Formula (II) or a pharmaceutically acceptable salt or solvate thereof, wherein R 9a and R 9b are combined to form a C 2- 9 heterocycloalkyl optionally substituted with one, two, or three groups selected from from halogen, C 1-6 alkyl, and C 1-6 haloalkyl.
  • provided herein is a compound of Formula (I) , (I’) , (Ia) , or (II) , or a pharmaceutically acceptable salt or solvate thereof, wherein X is -C (R 6 ) (R 6a ) -.
  • provided herein is a compound of Formula (I) , (I’) , (Ia) , or (II) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 6 and R 6a are hydrogen.
  • provided herein is a compound of Formula (I) , (I’) , (Ia) , or (II) , or a pharmaceutically acceptable salt or solvate thereof, wherein X is -O-.
  • X is selected from -O-and -N (R 7 ) -;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • R 8a , R 8b , R 8c , R 8d , R 8e , R 9b , and R 9c are each independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 ,
  • R 9a is selected from hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, and -OR 14 ;
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • R 14 is selected from C 1-6 alkyl and C 3-6 cycloalkyl; and each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11
  • provided herein is a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 9b is selected from hydrogen, halogen, and C 1-6 alkyl.
  • R 9b is hydrogen.
  • provided herein is a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 9a is -OR 14 .
  • provided herein is a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 14 is C 1-6 alkyl.
  • provided herein is a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 9a is -OCH 3 .
  • provided herein is a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein X is -O-.
  • provided herein is a compound of Formula (II) or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 8a and R 8e are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 8a and R 8e are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 8a and R 8e are independently selected from hydrogen and -OR 10 .
  • provided herein is a compound of Formula (II) or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 8a and R 8e are -OR 10 .
  • provided herein is a compound of Formula (II) or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 is C 1-6 alkyl. In some embodiments, provided herein is a compound of Formula (II) or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 is -CH 3 . In some embodiments, provided herein is a compound of Formula (II) or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 8b , R 8c , R 8d , and R 9c are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • provided herein is a compound of Formula (II) or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 8b , R 8c , R 8d , and R 9c are independently selected from hydrogen, halogen, and C 1-6 alkyl.
  • provided herein is a compound of Formula (II) or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 8b , R 8c , R 8d , and R 9c are hydrogen.
  • R 2 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N
  • R 1 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R
  • R 2b and R 3b are taken together to form a C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1- 9 heteroaryl; wherein C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, three, or four groups selected from R 15e ;
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O)
  • each R 10 is independently hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 12 is independently hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 13 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • R 2 is C 1-9 heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N
  • R 1 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • X is -C (R 6 ) (R 6a ) -, -S-, -O-, or -N (R 7 ) -;
  • R 6 and R 6a are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C (O
  • R 6 and R 6a are taken together to form an oxo
  • R 7 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • Ring A is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl;
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O)
  • n 0-6;
  • each R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 12 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 13 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • R 2 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N
  • R 1 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • X is -C (R 6 ) (R 6a ) -, -S-, -O-, or -N (R 7 ) -;
  • R 6 and R 6a are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C (O
  • R 6 and R 6a are taken together to form an oxo
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • Ring B is C 3-6 cycloalkyl, C 6-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl;
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O)
  • n 0-6;
  • each R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 12 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 13 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • provided herein is a compound of Formula (I) , (I’) , (Ia) , (II) , or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is unsubstituted pyrazolyl.
  • a compound of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is unsubstituted pyridinyl.
  • provided herein is a compound of Formula (I) , (I’) , (Ia) , (II) , or (III) , or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is unsubstituted pyrazolyl.
  • a compound of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is unsubstituted pyridinyl.
  • disclosed herein are compounds of Table 1A, Table 1B and Table 1C, or a pharmaceutically acceptable salt or solvate thereof.
  • a pharmaceutical composition comprising a compound of Table 1A, Table 1B and Table 1C, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.
  • composition comprising a compound of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) , or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.
  • a method of treating cancer in a mammal in need thereof comprising administering to the mammal a compound of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) , or a pharmaceutically acceptable salt or solvate thereof.
  • a method of treating cancer in a mammal in need thereof comprising administering to the mammal a compound of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) , or a pharmaceutically acceptable salt or solvate thereof, wherein the cancer is selected from lung cancer, mesothelioma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, stomach cancer, hepatocellular carcinoma, colon cancer, breast cancer, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, Hodgkin’s disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue,
  • a method of treating cancer in a mammal in need thereof comprising administering to the mammal a compound of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) , or a pharmaceutically acceptable salt or solvate thereof, wherein the cancer is selected from ER-positive breast cancer, glioblastoma, non-small cell lung cancer (NSCLC) , small cell lung cancer (SCLC) , melanoma, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer (CRC) , hepatocellular carcinoma (HCC) , renal cell carcinoma (RCC) , leukemia, lymphoma or multiple myeloma, acute lymphocytic leukemia (ALL) , acute myeloid leukemia (AML) , chronic lymphocytic leukemia (CLL) , chronic myeloid leukemia (CML
  • a method of treating cancer in a mammal in need thereof comprising administering to the mammal a compound of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) , or a pharmaceutically acceptable salt or solvate thereof, wherein the cancer is a solid tumor with KAT6A/6B amplification or overexpression, or leukemia or solid tumor with KAT6A/6B fusion protein resulting from chromosomal translocation.
  • Carboxyl refers to -COOH.
  • Cyano refers to -CN.
  • Alkyl refers to a straight-chain, or branched-chain saturated hydrocarbon monoradical having from one to about ten carbon atoms, more preferably one to six carbon atoms. Examples include, but are not limited to methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2, 2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2, 2-dimethyl-1-butyl, 3, 3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopent
  • a numerical range such as “C 1 -C 6 alkyl” or “C 1 - 6 alkyl” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated.
  • the alkyl is a C 1 - 10 alkyl.
  • the alkyl is a C 1 - 6 alkyl.
  • the alkyl is a C 1 - 5 alkyl.
  • the alkyl is a C 1 - 4 alkyl.
  • the alkyl is a C 1 - 3 alkyl.
  • an alkyl group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like.
  • the alkyl is optionally substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH 2 , or -NO 2 .
  • the alkyl is optionally substituted with halogen, -CN, -OH, or -OMe.
  • the alkyl is optionally substituted with halogen.
  • Alkenyl refers to a straight-chain, or branched-chain hydrocarbon monoradical having one or more carbon-carbon double-bonds and having from two to about ten carbon atoms, more preferably two to about six carbon atoms.
  • a numerical range such as “C 2 -C 6 alkenyl” or “C 2 - 6 alkenyl” means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkenyl” where no numerical range is designated.
  • an alkenyl group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like.
  • the alkenyl is optionally substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH 2 , or -NO 2 .
  • the alkenyl is optionally substituted with halogen, -CN, -OH, or -OMe.
  • the alkenyl is optionally substituted with halogen.
  • Alkynyl refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon triple-bonds and having from two to about ten carbon atoms, more preferably from two to about six carbon atoms. Examples include, but are not limited to ethynyl, 2-propynyl, 2-butynyl, 1, 3-butadiynyl and the like.
  • a numerical range such as “C 2 -C 6 alkynyl” or “C 2 - 6 alkynyl” means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkynyl” where no numerical range is designated.
  • an alkynyl group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like.
  • the alkynyl is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH 2 , or -NO 2 .
  • the alkynyl is optionally substituted with halogen, -CN, -OH, or -OMe.
  • the alkynyl is optionally substituted with halogen.
  • Alkylene refers to a straight or branched divalent hydrocarbon chain. Unless stated otherwise specifically in the specification, an alkylene group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the alkylene is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH 2 , or -NO 2 . In some embodiments, the alkylene is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkylene is optionally substituted with halogen.
  • Alkoxy refers to a radical of the formula -OR a where R a is an alkyl radical as defined. Unless stated otherwise specifically in the specification, an alkoxy group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the alkoxy is optionally substituted with halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH 2 , or -NO 2 . In some embodiments, the alkoxy is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkoxy is optionally substituted with halogen.
  • Aryl refers to a radical derived from a hydrocarbon ring system comprising 6 to 30 carbon atoms and at least one aromatic ring.
  • the aryl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems.
  • the aryl is a 6-to 10-membered aryl.
  • the aryl is a 6-membered aryl (phenyl) .
  • Aryl radicals include, but are not limited to, aryl radicals derived from the hydrocarbon ring systems of anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene.
  • an aryl may be optionally substituted, for example, with halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like.
  • the aryl is optionally substituted with halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 .
  • the aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, the aryl is optionally substituted with halogen.
  • Cycloalkyl refers to a partially or fully saturated, monocyclic or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or a heteroaryl ring, the cycloalkyl is bonded through a non-aromatic ring atom) , spiro, or bridged ring systems. In some embodiments, the cycloalkyl is fully saturated.
  • Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to fifteen carbon atoms (C 3 -C 15 fully saturated cycloalkyl or C 3 -C 15 cycloalkenyl) , from three to ten carbon atoms (C 3 -C 10 fully saturated cycloalkyl or C 3 -C 10 cycloalkenyl) , from three to eight carbon atoms (C 3 -C 8 fully saturated cycloalkyl or C 3 -C 8 cycloalkenyl) , from three to six carbon atoms (C 3 -C 6 fully saturated cycloalkyl or C 3 -C 6 cycloalkenyl) , from three to five carbon atoms (C 3 -C 5 fully saturated cycloalkyl or C 3 -C 5 cycloalkenyl) , or three to four carbon atoms (C 3 -C 4 fully saturated cycloalkyl or C 3 -C
  • the cycloalkyl is a 3-to 10-membered fully saturated cycloalkyl or a 3-to 10-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 3-to 6-membered fully saturated cycloalkyl or a 3-to 6-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 5-to 6-membered fully saturated cycloalkyl or a 5-to 6-membered cycloalkenyl.
  • Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.
  • Polycyclic cycloalkyls include, for example, adamantyl, norbornyl, decalinyl, bicyclo [3.3.0] octane, bicyclo [4.3.0] nonane, cis-decalin, trans-decalin, bicyclo [2.1.1] hexane, bicyclo [2.2.1] heptane, bicyclo [2.2.2] octane, bicyclo [3.2.2] nonane, and bicyclo [3.3.2] decane, and 7, 7-dimethyl-bicyclo [2.2.1] heptanyl.
  • Partially saturated cycloalkyls include, for example cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.
  • a cycloalkyl is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like.
  • a cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 .
  • a cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe.
  • the cycloalkyl is optionally substituted with halogen.
  • Halo or “halogen” refers to bromo, chloro, fluoro or iodo. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro.
  • Haloalkyl refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above, e.g., trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2, 2, 2-trifluoroethyl, 1, 2-difluoroethyl, 3-bromo-2-fluoropropyl, 1, 2-dibromoethyl, and the like.
  • “Hydroxyalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Hydroxyalkyl include, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.
  • Aminoalkyl refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Aminoalkyl include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl.
  • Heteroalkyl refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen (e.g., -NH-, -N (alkyl) -) , sulfur, phosphorus, or combinations thereof.
  • a heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl.
  • a heteroalkyl is a C 1 -C 6 heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or more atoms other than carbon, e.g., oxygen, nitrogen (e.g.
  • heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl.
  • heteroalkyl are, for example, -CH 2 OCH 3 , -CH 2 CH 2 OCH 3 , -CH 2 CH 2 OCH 2 CH 2 OCH 3 , -CH (CH 3 ) OCH 3 , -CH 2 NHCH 3 , -CH 2 N (CH 3 ) 2 , -CH 2 CH 2 NHCH 3 , or -CH 2 CH 2 N (CH 3 ) 2 .
  • a heteroalkyl is optionally substituted for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like.
  • a heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 .
  • a heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, the heteroalkyl is optionally substituted with halogen.
  • Heterocycloalkyl refers to a 3-to 24-membered partially or fully saturated ring radical comprising 2 to 23 carbon atoms and from one to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, silicon, and sulfur. In some embodiments, the heterocycloalkyl is fully saturated. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heterocycloalkyl comprises one to three nitrogens. In some embodiments, the heterocycloalkyl comprises one or two nitrogens.
  • the heterocycloalkyl comprises one nitrogen. In some embodiments, the heterocycloalkyl comprises one nitrogen and one oxygen.
  • the heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused (when fused with an aryl or a heteroaryl ring, the heterocycloalkyl is bonded through a non-aromatic ring atom) , spiro, or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized.
  • heterocycloalkyls include, but are not limited to, heterocycloalkyls having from two to fifteen carbon atoms (C 2 -C 15 fully saturated heterocycloalkyl or C 2 -C 15 heterocycloalkenyl) , from two to ten carbon atoms (C 2 -C 10 fully saturated heterocycloalkyl or C 2 -C 10 heterocycloalkenyl) , from two to eight carbon atoms (C 2 -C 8 fully saturated heterocycloalkyl or C 2 -C 8 heterocycloalkenyl) , from two to seven carbon atoms (C 2 -C 7 fully saturated heterocycloalkyl or C 2 -C 7 heterocycloalkenyl) , from two to six carbon atoms (C 2 -C 6 fully saturated heterocycloalkyl or C 2 -C 7 heterocycloalkenyl) , from two to five carbon atoms (C 2 -C 5 fully saturated heterocycloalkyl or C 2 -C 5
  • heterocycloalkyl radicals include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, dioxolanyl, thienyl [1, 3] dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl
  • heterocycloalkyl also includes all ring forms of the carbohydrates, including but not limited to the monosaccharides, the disaccharides and the oligosaccharides.
  • heterocycloalkyls have from 2 to 10 carbons in the ring. It is understood that when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including the heteroatoms) that make up the heterocycloalkyl (i.e. skeletal atoms of the heterocycloalkyl ring) .
  • the heterocycloalkyl is a 3-to 8-membered fully saturated heterocycloalkyl.
  • the heterocycloalkyl is a 3-to 7-membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3-to 6-membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 4-to 6-membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5-to 6-membered fully saturated heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3-to 8-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3-to 7-membered heterocycloalkenyl.
  • the heterocycloalkyl is a 3-to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 4-to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 5-to 6-membered heterocycloalkenyl.
  • a heterocycloalkyl may be optionally substituted as described below, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like.
  • the heterocycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 .
  • the heterocycloalkyl is optionally substituted with halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, the heterocycloalkyl is optionally substituted with halogen.
  • Heteroaryl refers to a 5-to 14-membered ring system radical comprising one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, and sulfur, and at least one aromatic ring.
  • the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur.
  • the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen.
  • the heteroaryl comprises one to three nitrogens.
  • the heteroaryl comprises one or two nitrogens.
  • the heteroaryl comprises one nitrogen.
  • the heteroaryl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is bonded through an aromatic ring atom) or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized.
  • the heteroaryl is a 5-to 10-membered heteroaryl.
  • the heteroaryl is a 5-to 6-membered heteroaryl.
  • the heteroaryl is a 6-membered heteroaryl.
  • the heteroaryl is a 5-membered heteroaryl.
  • examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo [b] [1, 4] dioxepinyl, 1, 4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl) , benzotriazolyl, benzo [4, 6] imidazo [1, 2-a] pyridinyl, carbazolyl, cinnolinyl,
  • a heteroaryl may be optionally substituted, for example, with halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like.
  • the heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 .
  • the heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, the heteroaryl is optionally substituted with halogen.
  • an optionally substituted group may be un-substituted (e.g., -CH 2 CH 3 ) , fully substituted (e.g., -CF 2 CF 3 ) , mono-substituted (e.g., -CH 2 CH 2 F) or substituted at a level anywhere in-between fully substituted and mono-substituted (e.g., -CH 2 CHF 2 , -CH 2 CF 3 , -CF 2 CH 3 , -CFHCHF 2 , etc. ) .
  • any substituents described should generally be understood as having a maximum molecular weight of about 1,000 daltons, and more typically, up to about 500 daltons.
  • an “effective amount” or “therapeutically effective amount” refers to an amount of a compound administered to a mammalian subject, either as a single dose or as part of a series of doses, which is effective to produce a desired therapeutic effect.
  • Treatment of an individual (e.g. a mammal, such as a human) or a cell is any type of intervention used in an attempt to alter the natural course of the individual or cell.
  • treatment includes administration of a pharmaceutical composition, subsequent to the initiation of a pathologic event or contact with an etiologic agent and includes stabilization of the condition (e.g., condition does not worsen) or alleviation of the condition.
  • Described herein are compounds of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) , or a pharmaceutically acceptable salt or solvate thereof, which are KAT6A inhibitors and useful in the treatment of a disease or disorder associated with KAT6A inhibition.
  • the compounds of Formula (I) , (I’) , (Ia) , (II) , (III) , (IV) , (V) or (VI) , or a pharmaceutically acceptable salt or solvate thereof are useful in the treatment of cancer.
  • Y 1 is CR 1a or N
  • Y 2 is CR 2a or N
  • Y 3 is CR 3a or N
  • Y 4 is CR 4a or N
  • Y 5 is CR 5a or N
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N; wherein at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N;
  • X is selected from -C (R 6 ) (R 6a ) -, -O-, and -N (R 7 ) -;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R
  • R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1- 9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (
  • Y 1 is CR 1a . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Y 1 is N.
  • Y 2 is CR 2a . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Y 2 is N.
  • Y 3 is CR 3a . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Y 3 is N.
  • Y 4 is CR 4a . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Y 4 is N.
  • Y 5 is CR 5a . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Y 5 is N.
  • Y 1 is CR 1a and Y 5 is CR 5a .
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are independently selected from hydrogen and -OR 10 .
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are -OR 10
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are -OR 10
  • R 10 is C 1-6 alkyl.
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are -OR 10
  • R 10 is -CH 3 .
  • Z 1 is CR 1b . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Z 1 is N.
  • Z 2 is CR 2b . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Z 2 is N.
  • Z 3 is CR 3b . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Z 3 is N.
  • Y 1 is CR 1a ; Y 2 is N; Y 3 is CR 3a ; Y 4 is CR 4a ; Y 5 is CR 5a ; Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Y 1 is CR 1a ; Y 2 is N; Y 3 is CR 3a ; Y 4 is CR 4a ; Y 5 is CR 5a ; Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N.
  • R 1a and R 5a are -OR 10 .
  • R 1a and R 5a are independently selected from -O-C 1-6 alkyl and -O-C 1- 6 haloalkyl.
  • R 1a and R 5a are -OCH 3 .
  • Y 2 is N; Y 3 is CR 3a ; and Y 4 is CR 4a .
  • Y 2 is CR 2a ; Y 3 is N; and Y 4 is CR 4a .
  • Y 2 is N; Y 3 is CR 3a ; and Y 4 is N.
  • Y 2 is CR 2a ; Y 3 is CR 3a ; and Y 4 is N.
  • Y 2 is CR 2a ; Y 3 is CR 3a ; and Y 4 is CR 4a .
  • Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Z 1 is N; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Z 1 is CR 1b ; Z 2 is N; and Z 3 is CR 3b .
  • Z 1 is CR 1b ; Z 2 is N; and Z 3 is CR 3b .
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, and C 1-6 alkyl.
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are hydrogen.
  • R 1b and R 2b are hydrogen, R 3b is -OR 10 , and R 10 is C 1-6 alkyl.
  • R 1b and R 2b are hydrogen, R 3b is -OR 10 , R 10 is C 1-6 alkyl substituted with one, two, or three halogen.
  • R 1a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 1a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 1a is hydrogen.
  • R 1a is C 1-6 alkyl.
  • R 1a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 1a is C 1-6 alkoxyl.
  • In some 1a is -OCF 3 .
  • R 2a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 2a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 2a is hydrogen.
  • R 2a is C 1-6 alkyl.
  • R 2a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, are C 2-9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from R 15b .
  • R 3a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 cycloalkyl, wherein the C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, and C 3-6 cycloalkyl are optionally substituted.
  • R 3a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-6 alkynyl.
  • R 3a is hydrogen.
  • R 3a is C 1-6 alkyl.
  • R 3a is C 1-6 alkyl.
  • R 3a is C 1-6 haloalkyl.
  • R 3a is C 2-6 alkenyl.
  • R 3a is C 2-6 alkynyl.
  • R 4a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 4a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 4a is hydrogen.
  • R 4a is C 1-6 alkyl.
  • R 4a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or-OR 10 .
  • R 5a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is hydrogen.
  • R 5a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is C 1-6 alkoxyl.
  • R 5a is C 1-3 alkoxyl.
  • R 5a is -OCH 3 .
  • R 1b is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 1b is hydrogen.
  • R 1b is halogen.
  • R 1b is C 1-6 alkyl.
  • R 1b is C 1-6 haloalkyl.
  • R 2b is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 2b is hydrogen.
  • R 2b is halogen.
  • R 1b is C 1-6 alkyl.
  • R 1b is C 1-6 haloalkyl.
  • R 3b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 3b is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3b is hydrogen.
  • R 3b is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3b is C 1-6 alkoxyl.
  • R 3b is C 1-3 alkoxyl. In some embodiments, R 3b is C 1-3 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen. In some embodiments, R 3b is -OCH 3 . In some embodiments, R 3b is -OCH 2 F. In some embodiments, R 3b is -OCF 3 . In some embodiments, R 3b is -OCHF 2 . In some embodiments, R 3b is -OCH 2 CF 3 .
  • X is -C (R 6 ) (R 6a ) -. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, X is -C (R 6 ) (R 6a ) -and R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, and -OH. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, X is -C (R 6 ) (R 6a ) -and R 6 and R 6a are hydrogen.
  • X is -O-.
  • X is -N (R 7 ) -. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is hydrogen. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is C 1-6 alkyl.
  • R 1 is optionally substituted C 1-9 heteroaryl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 membered heteroaryl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 6 membered heteroaryl.
  • R 1 is monocyclic heteroaryl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is bicyclic heteroaryl. In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from R 15a . In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxyl.
  • R 1 is optionally substituted with one, two, or three groups selected from oxo, -CN, amino, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1- 6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted.
  • R 1 is unsubstituted pyrazolyl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted imidazolyl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl.
  • R 1 is unsubstituted pyridinyl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted thiazolyl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.
  • R 1 is selected from In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is or
  • a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof, is selected from
  • R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl. In some embodiments, R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl, wherein C 1-6 alkyl and C 3-6 cycloalkyl are optionally substituted with one, two, or three groups selected from halogen. hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl. In some embodiments, R 10 is C 1-6 alkyl or C 1-6 haloalkyl.
  • R 10 is hydrogen. In some embodiments, R 10 is -CH 3 . In some embodiments, R 10 is -CH 2 F. In some embodiments, R 10 is -CHF 2 . In some embodiments, R 10 is -CH 2 CF 3 . In some embodiments, R 10 is -CF 3 .
  • R 11 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 11 is hydrogen. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 11 is C 1-6 alkyl.
  • R 12 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 12 is hydrogen. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 12 is C 1-6 alkyl.
  • R 13 is C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl. In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, R 13 is C 1- 6 alkyl or C 1-6 haloalkyl.
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, - CN, C 1-6 alkyl, C 1-6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1- 6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (I) , each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (I) , each R 15a , each R 15b , and each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (I) , each R 15a , each R 15b , and each R 15c are independently -OR 10 .
  • Y 2 is CR 2a or N
  • Y 3 is CR 3a or N
  • Y 4 is CR 4a or N
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N; wherein at least one of Y 2 , Y 3 , Y 4 , Z 1 , Z 2 , and Z 3 is N;
  • X is selected from -C (R 6 ) (R 6a ) -, -O-, and -N (R 7 ) -;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R
  • R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1- 9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (
  • R 1a and R 5a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 . In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1a and R 5a are independently selected from hydrogen and -OR 10 . In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1a and R 5a are -OR 10 .
  • R 1a and R 5a are -OR 10
  • R 10 is C 1-6 alkyl.
  • R 1a and R 5a are -OR 10
  • R 10 is -CH 3 .
  • Y 2 is N; Y 3 is CR 3a ; and Y 4 is CR 4a .
  • Y 2 is CR 2a ; Y 3 is N; and Y 4 is CR 4a .
  • Y 2 is N; Y 3 is CR 3a ; and Y 4 is N.
  • Y 2 is CR 2a ; Y 3 is CR 3a ; and Y 4 is N.
  • Y 2 is CR 2a ; Y 3 is CR 3a ; and Y 4 is CR 4a .
  • Y 2 is CR 2a . In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, Y 2 is N.
  • Y 3 is CR 3a . In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, Y 3 is N.
  • Y 4 is CR 4a . In some embodiments of a compound of Formula (I) , or a pharmaceutically acceptable salt or solvate thereof, Y 4 is N.
  • Y 2 is N; Y 3 is CR 3a ; and Y 4 is CR 4a .
  • Y 2 is CR 2a ; Y 3 is N; and Y 4 is CR 4a .
  • Y 2 is N; Y 3 is CR 3a ; and Y 4 is N.
  • Y 2 is CR 2a ; Y 3 is CR 3a ; and Y 4 is N.
  • Y 2 is CR 2a ; Y 3 is CR 3a ; and Y 4 is CR 4a .
  • Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Z 1 is N; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Z 1 is CR 1b ; Z 2 is N; and Z 3 is CR 3b .
  • Z 1 is CR 1b ; Z 2 is N; and Z 3 is CR 3b .
  • Z 1 is CR 1b . In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, Z 1 is N.
  • Z 2 is CR 2b . In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, Z 2 is N.
  • Z 3 is CR 3b . In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, Z 3 is N.
  • Y 1 is CR 1a ; Y 2 is N; Y 3 is CR 3a ; Y 4 is CR 4a ; Y 5 is CR 5a ; Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Y 1 is CR 1a ; Y 2 is N; Y 3 is CR 3a ; Y 4 is CR 4a ; Y 5 is CR 5a ; Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N.
  • R 1a and R 5a are -OR 10 .
  • R 1a and R 5a are independently selected from -O-C 1-6 alkyl and -O-C 1- 6 haloalkyl.
  • R 1a and R 5a are -OCH 3 .
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, and C 1-6 alkyl.
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are hydrogen.
  • R 1b and R 2b are hydrogen, R 3b is -OR 10 , and R 10 is C 1-6 alkyl.
  • R 1b and R 2b are hydrogen, R 3b is -OR 10 , R 10 is C 1-6 alkyl substituted with one, two, or three halogen.
  • R 1a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 1a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 1a is hydrogen.
  • R 1a is C 1-6 alkyl.
  • R 1a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 1a is C 1- 6 alkoxyl.
  • In some 1a is -OCF 3 .
  • R 2a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 2a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 2a is hydrogen.
  • R 2a is C 1-6 alkyl.
  • R 2a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, are C 2-9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from R 15b .
  • R 3a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 cycloalkyl, wherein the C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, and C 3-6 cycloalkyl are optionally substituted.
  • R 3a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-6 alkynyl.
  • R 3a is hydrogen.
  • R 3a is C 1-6 alkyl.
  • R 3a is C 1-6 alkyl.
  • R 3a is C 1-6 haloalkyl.
  • R 3a is C 2-6 alkenyl.
  • R 3a is C 2-6 alkynyl.
  • R 4a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 4a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 4a is hydrogen.
  • R 4a is C 1-6 alkyl.
  • R 4a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or-OR 10 .
  • R 5a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is hydrogen.
  • R 5a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is C 1-6 alkoxyl.
  • R 5a is C 1-3 alkoxyl.
  • R 5a is -OCH 3 .
  • R 1b is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 1b is hydrogen.
  • R 1b is halogen.
  • R 1b is C 1-6 alkyl.
  • R 1b is C 1-6 haloalkyl.
  • R 2b is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 2b is hydrogen.
  • R 2b is halogen.
  • R 1b is C 1-6 alkyl.
  • R 1b is C 1-6 haloalkyl.
  • R 3b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 3b is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3b is hydrogen.
  • R 3b is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3b is C 1-6 alkoxyl.
  • R 3b is C 1- 3 alkoxyl. In some embodiments, R 3b is C 1-3 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen. In some embodiments, R 3b is -OCH 3 . In some embodiments, R 3b is -OCH 2 F. In some embodiments, R 3b is -OCF 3 . In some embodiments, R 3b is -OCHF 2 . In some embodiments, R 3b is -OCH 2 CF 3 .
  • X is -C (R 6 ) (R 6a ) -. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, X is -C (R 6 ) (R 6a ) -and R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, and -OH. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, X is -C (R 6 ) (R 6a ) -and R 6 and R 6a are hydrogen.
  • X is -O-.
  • X is -N (R 7 ) -. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is hydrogen. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is C 1-6 alkyl.
  • R 1 is optionally substituted C 1-9 heteroaryl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 membered heteroaryl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 6 membered heteroaryl.
  • R 1 is monocyclic heteroaryl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is bicyclic heteroaryl. In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from R 15a . In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxyl.
  • R 1 is optionally substituted with one, two, or three groups selected from oxo, -CN, amino, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted.
  • R 1 is unsubstituted pyrazolyl.
  • R 1 is unsubstituted imidazolyl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridinyl.
  • R 1 is unsubstituted thiazolyl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.
  • R 1 is selected from
  • R 1 is
  • R 1 is In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is in some embodiments, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is in some embodiments, R 1 is
  • a compound of Formula (Ia) or a pharmaceutically acceptable salt or solvate thereof, is selected from
  • R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl. In some embodiments, R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl, wherein C 1- 6 alkyl and C 3-6 cycloalkyl are optionally substituted with one, two, or three groups selected from halogen. hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl. In some embodiments, R 10 is C 1-6 alkyl or C 1-6 haloalkyl.
  • R 10 is hydrogen. In some embodiments, R 10 is -CH 3 . In some embodiments, R 10 is -CH 2 F. In some embodiments, R 10 is -CHF 2 . In some embodiments, R 10 is -CH 2 CF 3 . In some embodiments, R 10 is -CF 3 .
  • R 11 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 11 is hydrogen. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 11 is C 1-6 alkyl.
  • R 12 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 12 is hydrogen. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 12 is C 1-6 alkyl.
  • R 13 is C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl. In some embodiments of a compound of Formula (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 13 is C 1-6 alkyl or C 1-6 haloalkyl.
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1- 6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (Ia) , each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (Ia) , each R 15a , each R 15b , and each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (Ia) , each R 15a , each R 15b , and each R 15c are independently -OR 10 .
  • Y 1 is CR 1a or N
  • Y 2 is CR 2a or N
  • Y 3 is CR 3a or N
  • Y 4 is CR 4a or N
  • Y 5 is CR 5a or N
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N
  • X is -O-or -S-;
  • X is selected from -C (R 6 ) (R 6a ) -and -N (R 7 ) -, wherein at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R
  • R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1- 9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , - OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N
  • X is -O-. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, X is -S-.
  • X is -O-or -S-.
  • X is -C (R 6 ) (R 6a ) -, wherein at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N.
  • X is -N (R 7 ) -, wherein at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N.
  • Y 1 is CR 1a or N
  • Y 2 is CR 2a or N
  • Y 3 is CR 3a or N
  • Y 4 is CR 4a or N
  • Y 5 is CR 5a or N
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N
  • X is -O-
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , - OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N
  • a compound of Formula (I’) has a structure of Formula (Ia) .
  • X is -O-. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, X is -S-. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, X is -C (R 6 ) (R 6a ) -. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -.
  • Y 1 is CR 1a . In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, Y 1 is N.
  • Y 2 is CR 2a . In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, Y 2 is N.
  • Y 3 is CR 3a . In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, Y 3 is N.
  • Y 4 is CR 4a . In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, Y 4 is N.
  • Y 5 is CR 5a . In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, Y 5 is N.
  • Y 1 is CR 1a and Y 5 is CR 5a .
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are independently selected from hydrogen and -OR 10 .
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are -OR 10
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are -OR 10
  • R 10 is C 1-6 alkyl.
  • Y 1 is CR 1a
  • Y 5 is CR 5a
  • R 1a and R 5a are -OR 10
  • R 10 is -CH 3 .
  • Y 2 is N; Y 3 is CR 3a ; and Y 4 is CR 4a .
  • Y 2 is CR 2a ; Y 3 is N; and Y 4 is CR 4a .
  • Y 2 is N; Y 3 is CR 3a ; and Y 4 is N.
  • Y 2 is CR 2a ; Y 3 is CR 3a ; and Y 4 is N.
  • Y 2 is CR 2a ; Y 3 is CR 3a ; and Y 4 is CR 4a .
  • Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Z 1 is N; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Z 1 is CR 1b ; Z 2 is N; and Z 3 is CR 3b .
  • Z 1 is CR 1b ; Z 2 is N; and Z 3 is CR 3b .
  • Z 1 is CR 1b . In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, Z 1 is N.
  • Z 2 is CR 2b . In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, Z 2 is N.
  • Z 3 is CR 3b . In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, Z 3 is N.
  • Y 1 is CR 1a ; Y 2 is N; Y 3 is CR 3a ; Y 4 is CR 4a ; Y 5 is CR 5a ; Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Y 1 is CR 1a ; Y 2 is N; Y 3 is CR 3a ; Y 4 is CR 4a ; Y 5 is CR 5a ; Z 1 is CR 1b ; Z 2 is CR 2b ; and Z 3 is CR 3b .
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , and Z 3 is N.
  • R 1a and R 5a are -OR 10 .
  • R 1a and R 5a are independently selected from -O-C 1-6 alkyl and -O-C 1- 6 haloalkyl.
  • R 1a and R 5a are -OCH 3 .
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are independently selected from hydrogen, halogen, and C 1-6 alkyl.
  • R 2a , R 3a , R 4a , R 1b , R 2b , and R 3b are hydrogen.
  • R 1b and R 2b are hydrogen, R 3b is -OR 10 , and R 10 is C 1-6 alkyl.
  • R 1b and R 2b are hydrogen, R 3b is -OR 10 , R 10 is C 1-6 alkyl substituted with one, two, or three halogen.
  • R 1a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 1a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 1a is hydrogen.
  • R 1a is C 1-6 alkyl.
  • R 1a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 1a is C 1-6 alkoxyl.
  • In some 1a is -OCF 3 .
  • R 2a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 2a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 2a is hydrogen.
  • R 2a is C 1-6 alkyl.
  • R 2a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, are C 2-9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from R 15b .
  • R 3a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 cycloalkyl, wherein the C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, and C 3-6 cycloalkyl are optionally substituted.
  • R 3a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-6 alkynyl.
  • R 3a is hydrogen.
  • R 3a is C 1-6 alkyl.
  • R 3a is C 1-6 alkyl.
  • R 3a is C 1-6 haloalkyl.
  • R 3a is C 2-6 alkenyl.
  • R 3a is C 2-6 alkynyl.
  • R 4a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 4a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 4a is hydrogen.
  • R 4a is C 1-6 alkyl.
  • R 4a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or-OR 10 .
  • R 5a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is hydrogen.
  • R 5a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 5a is C 1-6 alkoxyl.
  • R 5a is C 1-3 alkoxyl.
  • R 5a is -OCH 3 .
  • R 1b is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 1b is hydrogen.
  • R 1b is halogen.
  • R 1b is C 1-6 alkyl.
  • R 1b is C 1-6 haloalkyl.
  • R 2b is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 2b is hydrogen.
  • R 2b is halogen.
  • R 1b is C 1-6 alkyl.
  • R 1b is C 1-6 haloalkyl.
  • R 3b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 3b is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3b is hydrogen.
  • R 3b is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 3b is C 1-6 alkoxyl.
  • R 3b is C 1-3 alkoxyl. In some embodiments, R 3b is C 1-3 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen. In some embodiments, R 3b is -OCH 3 . In some embodiments, R 3b is -OCH 2 F. In some embodiments, R 3b is -OCF 3 . In some embodiments, R 3b is -OCHF 2 . In some embodiments, R 3b is -OCH 2 CF 3 .
  • X is -C (R 6 ) (R 6a ) -.
  • X is -C (R 6 ) (R 6a ) -and R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, and -OH.
  • X is -C (R 6 ) (R 6a ) -and R 6 and R 6a are hydrogen.
  • X is -O-.
  • X is -N (R 7 ) -. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is hydrogen. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is C 1-6 alkyl.
  • R 1 is optionally substituted C 1-9 heteroaryl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 membered heteroaryl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 6 membered heteroaryl.
  • R 1 is monocyclic heteroaryl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is bicyclic heteroaryl. In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from R 15a . In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxyl.
  • R 1 is optionally substituted with one, two, or three groups selected from oxo, -CN, amino, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1- 6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted.
  • R 1 is unsubstituted pyrazolyl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted imidazolyl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl.
  • R 1 is unsubstituted pyridinyl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted thiazolyl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.
  • R 1 is selected from In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is in some embodiments, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is
  • a compound of Formula (I’) or a pharmaceutically acceptable salt or solvate thereof, is selected from
  • R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl. In some embodiments, R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl, wherein C 1-6 alkyl and C 3-6 cycloalkyl are optionally substituted with one, two, or three groups selected from halogen. hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl. In some embodiments, R 10 is C 1-6 alkyl or C 1-6 haloalkyl.
  • R 10 is hydrogen. In some embodiments, R 10 is -CH 3 . In some embodiments, R 10 is -CH 2 F. In some embodiments, R 10 is -CHF 2 . In some embodiments, R 10 is -CH 2 CF 3 . In some embodiments, R 10 is -CF 3 .
  • R 11 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 11 is hydrogen. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 11 is C 1-6 alkyl.
  • R 12 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 12 is hydrogen. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 12 is C 1-6 alkyl.
  • R 13 is C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl. In some embodiments of a compound of Formula (I’) , or a pharmaceutically acceptable salt or solvate thereof, R 13 is C 1- 6 alkyl or C 1-6 haloalkyl.
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1- 6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (I’) , each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (I’) , each R 15a , each R 15b , and each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (I’) , each R 15a , each R 15b , and each R 15c are independently -OR 10 .
  • Z 1 is CR 1b
  • Z 2 is CR 2b
  • Z 3 is CR 3b
  • each R 1a and each R 5a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10
  • each R 2a , each R 3a , each R 4a , each R 1b , each R 2b , and each R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10
  • R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, or C 2-9 heterocycloalkyl.
  • R 1 is an optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is an optionally substituted 5 membered heteroaryl.
  • R 1 is pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, , wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is selected from In some embodiments of a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is selected from In some embodiments of a compound of Formula (I) , (I’) , or (Ia) , or a pharmaceutically acceptable salt or solvate thereof, R 10 is C 1-6 alkyl or C 1-6 haloalkyl.
  • X is selected from -C (R 6 ) (R 6a ) -, -O-, and -N (R 7 ) -;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1- 9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • R 8a , R 8b , R 8c , R 8d , R 8e , R 9b , and R 9c are each independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 ,
  • R 9a is selected from C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 14 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C (O) N
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • R 14 is independently selected from hydrogen, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 2-6 alkenyl, C 2-6 alkynyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl; and
  • each R 15a , each R 15b , each R 15c , each R 15d , and each R 15e are each independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) ,
  • R 8a and R 8e are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 . In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 8a and R 8e are independently selected from hydrogen and -OR 10 . In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 8a and R 8e are -OR 10 .
  • R 8a and R 8e are -OR 10 and R 10 is C 1-6 alkyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 8a and R 8e are -OR 10 and R 10 is -CH 3 .
  • R 8a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 8a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8a is hydrogen.
  • R 8a is C 1-6 alkyl.
  • R 8a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8a is C 1-6 alkoxyl.
  • R 8a is -OCF 3 .
  • R 8e is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 8e is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8e is hydrogen.
  • R 8e is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8e is C 1-6 alkoxyl.
  • R 8e is C 1-3 alkoxyl.
  • R 8e is -OCH 3 .
  • R 8b , R 8c , R 8d , and R 9c are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 8b , R 8c , R 8d , and R 9c are independently selected from hydrogen, halogen, and C 1-6 alkyl.
  • R 8b , R 8c , R 8d , and R 9c are hydrogen.
  • R 8b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 8b is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8b is hydrogen.
  • R 8b is C 1-6 alkyl.
  • R 8b is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8c is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, are C 2-9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from R 15b .
  • R 8c is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 cycloalkyl, wherein the C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, and C 3-6 cycloalkyl are optionally substituted.
  • R 8c is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-6 alkynyl.
  • R 8c is hydrogen.
  • R 8c is C 1-6 alkyl.
  • R 8c is C 1-6 alkyl.
  • R 8c is C 1-6 haloalkyl.
  • R 8c is C 2-6 alkenyl.
  • R 8c is C 2-6 alkynyl.
  • R 8d is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 8d is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8d is hydrogen.
  • R 8d is C 1-6 alkyl.
  • R 8d is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 9c is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 9c is hydrogen.
  • R 9c is halogen.
  • R 9c is C 1-6 alkyl.
  • R 9c is C 1-6 haloalkyl.
  • R 9b is selected from hydrogen, halogen, and C 1-6 alkyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 9b is hydrogen. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 9b is halogen. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 9b is C 1- 6 alkyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 9b is -CH 3 .
  • R 9b is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 9b is hydrogen.
  • R 9b is halogen.
  • R 9b is C 1-6 alkyl.
  • R 9b is C 1-6 haloalkyl.
  • R 9a is -OR 14 . In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 9a is -OR 14 and R 14 is C 1-6 haloalkyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 9a is -OR 14 and R 14 is -CF 3 . In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 9a is -OR 14 and R 14 is -CHF 2 .
  • R 9a is C 3-6 cycloalkyl are substituted with one, two, or three groups selected from R 15c .
  • R 9a is C 3-6 cycloalkyl are substituted with one, two, or three groups selected from R 15c and each R 15c is independently selected from halogen, C 1-6 alkyl, C 1- 6 haloalkyl.
  • R 9a is C 3-6 cycloalkyl are substituted with one, two, or three groups selected from R 15c and each R 15c is halogen.
  • R 9a is C 1-6 alkyl, C 1-6 haloalkyl, or -OR 14 .
  • R 9a is C 1- 6 alkyl, C 1-6 haloalkyl, or -O-C 1-6 haloalkyl.
  • R 9a is -O-C 1-6 haloalkyl.
  • R 9a is -O-C 1-6 haloalkyl.
  • R 9a is -OCH 2 F.
  • R 9a and R 9b are combined to form a C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, or C 2-9 heteroaryl, wherein C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, and C 2-9 heteroaryl are optionally substituted with one, two, or three groups selected from R 15e .
  • R 9a and R 9b are combined to form a C 2-9 heterocycloalkyl optionally substituted with one, two, or three groups selected from R 15e .
  • R 9a and R 9b are combined to form a C 2- 9 heterocycloalkyl optionally substituted with one, two, or three groups selected from from halogen, C 1-6 alkyl, and C 1-6 haloalkyl.
  • R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl.
  • R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3- 6 cycloalkyl, wherein C 1-6 alkyl and C 3-6 cycloalkyl are optionally substituted with one, two, or three groups selected from halogen. hydrogen.
  • R 10 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl.
  • R 10 is C 1-6 alkyl or C 1-6 haloalkyl.
  • R 10 is hydrogen.
  • R 10 is -CH 3 .
  • R 10 is -CH 2 F.
  • R 10 is -CHF 2 .
  • R 10 is -CH 2 CF 3 .
  • R 10 is -CF 3 .
  • R 9a and R 9b are combined to form a 5 to 7-membered ring. In some embodiments, R 9a and R 9b are combined to form a 6-membered ring. In some embodiments, R 9a and R 9b are combined to form a cycloalkyl. In some embodiments, R 9a and R 9b are combined to form a heterocycloalkyl. In some embodiments, R 9a and R 9b are combined to form a ring containing 1 or 2 oxygen and 0-2 nitrogen. In some embodiments, R 9a and R 9b are combined to form a ring containing 1 oxygen.
  • a compound of Formula (II) is In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, is in some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, is
  • R 11 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 11 is hydrogen. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 11 is C 1-6 alkyl.
  • R 12 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 12 is hydrogen. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 12 is C 1-6 alkyl.
  • R 13 is C 1-6 haloalkyl, C 1-6 alkyl or C 3-6 cycloalkyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 13 is C 1- 6 alkyl.
  • R 14 is hydrogen, C 1-6 haloalkyl, or C 3-6 cycloalkyl. In some embodiments, R 14 is hydrogen, or C 1-6 haloalkyl. In some embodiments, R 14 is C 1-6 haloalkyl. In some embodiments, R 14 is hydrogen. In some embodiments, R 14 is -CH 2 F. In some embodiments, R 14 is -CH 2 CF 3 . In some embodiments, R 14 is -CF 3 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, - CN, C 1-6 alkyl, C 1-6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1- 6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (II) , each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (II) , each R 15a , each R 15b , and each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (II) , each R 15a , each R 15b , and each R 15c are independently -OR 10 .
  • X is -C (R 6 ) (R 6a ) -. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, X is -C (R 6 ) (R 6a ) -and R 6 and R 6a are independently selected from hydrogen, halogen, C 1-6 alkyl, and -OH. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, X is -C (R 6 ) (R 6a ) -and R 6 and R 6a are hydrogen.
  • X is -O-.
  • X is -N (R 7 ) -. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is hydrogen. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is C 1-6 alkyl.
  • R 1 is optionally substituted C 1-9 heteroaryl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 membered heteroaryl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 6 membered heteroaryl.
  • R 1 is monocyclic heteroaryl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is bicyclic heteroaryl. In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from R 15a . In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxyl.
  • R 1 is optionally substituted with one, two, or three groups selected from oxo, -CN, amino, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1- 6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted.
  • R 1 is unsubstituted pyrazolyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted imidazolyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl.
  • R 1 is unsubstituted pyridinyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted thiazolyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.
  • R 1 is selected from In some embodiments of a compound of Formula (II) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is in some embodiments, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is
  • X is selected from -O-and -N (R 7 ) -;
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a ;
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • R 8a , R 8b , R 8c , R 8d , R 8e , R 9b , and R 9c are each independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 ,
  • R 9a is selected from hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, and -OR 14 ;
  • each R 10 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6- 10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 12 is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl;
  • each R 13 is independently selected C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • R 14 is selected from C 1-6 alkyl and C 3-6 cycloalkyl
  • each R 15a and each R 15b are each independently selected from halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (
  • R 8a and R 8e are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 . In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 8a and R 8e are independently selected from hydrogen and -OR 10 . In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 8a and R 8e are -OR 10 .
  • R 8a and R 8e are -OR 10 and R 10 is C 1-6 alkyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 8a and R 8e are -OR 10 and R 10 is -CH 3 .
  • R 8a is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 8a is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8a is hydrogen.
  • R 8a is C 1-6 alkyl.
  • R 8a is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8a is C 1- 6 alkoxyl.
  • R 8a is -OCF 3 .
  • R 8e is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 8e is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8e is hydrogen.
  • R 8e is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8e is C 1-6 alkoxyl.
  • R 8e is C 1-3 alkoxyl.
  • R 8e is -OCH 3 .
  • R 8b , R 8c , R 8d , and R 9c are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 8b , R 8c , R 8d , and R 9c are independently selected from hydrogen, halogen, and C 1-6 alkyl.
  • R 8b , R 8c , R 8d , and R 9c are hydrogen.
  • R 8b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 8b is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8b is hydrogen.
  • R 8b is C 1-6 alkyl.
  • R 8b is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8c is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, are C 2-9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from R 15b .
  • R 8c is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 cycloalkyl, wherein the C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, and C 3-6 cycloalkyl are optionally substituted.
  • R 8c is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-6 alkynyl.
  • R 8c is hydrogen.
  • R 8c is C 1-6 alkyl.
  • R 8c is C 1-6 alkyl.
  • R 8c is C 1-6 haloalkyl.
  • R 8c is C 2-6 alkenyl.
  • R 8c is C 2-6 alkynyl.
  • R 8d is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • R 8d is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 8d is hydrogen.
  • R 8d is C 1-6 alkyl.
  • R 8d is C 1-6 alkoxyl, wherein the alkoxyl is optionally substituted with 1, 2 or 3 halogen.
  • R 9c is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 9c is hydrogen.
  • R 9c is halogen.
  • R 9c is C 1-6 alkyl.
  • R 9c is C 1-6 haloalkyl.
  • R 9b is selected from hydrogen, halogen, and C 1-6 alkyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9b is hydrogen. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9b is halogen. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9b is C 1- 6 alkyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9b is -CH 3 .
  • R 9b is hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl, wherein C 1-6 alkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 9b is hydrogen.
  • R 9b is halogen.
  • R 9b is C 1-6 alkyl.
  • R 9b is C 1-6 haloalkyl.
  • R 9a is -OR 14 . In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9a is -OR 14 and R 14 is C 1-6 alkyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9a is -OR 14 and R 14 is -CH 3 . In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9a is -OR 14 and R 14 is C 3- 6 cycloalkyl. In some embodiments, R 9a is -OCH 2 F.
  • R 9a is C 1-6 alkyl, C 3-6 cycloalkyl, or -OR 14 . In some embodiments, R 9a is C 1-6 alkyl, C 1-6 cycloalkyl, or C 1-6 alkoxyl, In some embodiments, R 9a is C 1- 6 alkoxyl. In some embodiments, R 9a is C 1-3 alkoxyl.
  • R 9a is hydrogen. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9a is C 1-6 alkyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 9a is C 3-6 cycloalkyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, X is -O-.
  • X is -N (R 7 ) -. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is hydrogen. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, X is -N (R 7 ) -and R 7 is C 1-6 alkyl.
  • R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl. In some embodiments, R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl, wherein C 1- 6 alkyl and C 3-6 cycloalkyl are optionally substituted with one, two, or three groups selected from halogen. hydrogen. In some embodiments, R 10 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl. In some embodiments, R 10 is C 1-6 alkyl or C 1-6 haloalkyl.
  • R 10 is hydrogen. In some embodiments, R 10 is -CH 3 . In some embodiments, R 10 is -CH 2 F. In some embodiments, R 10 is -CHF 2 . In some embodiments, R 10 is -CH 2 CF 3 . In some embodiments, R 10 is -CF 3 .
  • R 11 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 11 is hydrogen. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 11 is C 1-6 alkyl.
  • R 12 is hydrogen, C 1-6 alkyl, and C 1-6 haloalkyl. In some embodiments, R 12 is hydrogen. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 12 is C 1-6 alkyl.
  • R 13 is C 1-6 halaoalkyl, C 1-6 alkyl or C 3-6 cycloalkyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 13 is C 1-6 alkyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 13 is C 1-6 halaoalkyl.
  • R 14 is C 1-6 alkyl or C 3-6 cycloalkyl. In some embodiments, R 14 is C 1-6 alkyl. In some embodiments, R 14 is C 3-6 cycloalkyl. In some embodiments, R 14 is -CH 3 .
  • each R 15a and each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a and each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a and each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a and each R 15b are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a and each R 15b are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (III) , each R 15a and each R 15b are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (III) , each R 15a and each R 15b are independently halogen, C 1-6 alkyl, or -OR 10 .
  • each R 15a and each R 15b are independently C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (III) , each R 15a and each R 15b are independently C 1- 6 alkyl or -OR 10 . In some embodiments of a compound of Formula (III) , each R 15a and each R 15b are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (III) , each R 15a and each R 15b are independently -OR 10 .
  • R 1 is optionally substituted C 1-9 heteroaryl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 membered heteroaryl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 6 membered heteroaryl.
  • R 1 is monocyclic heteroaryl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is bicyclic heteroaryl. In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from R 15a . In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxyl.
  • R 1 is optionally substituted with one, two, or three groups selected from oxo, -CN, amino, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are unsubstituted.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, and pyridinyl are unsubstituted.
  • R 1 is unsubstituted pyrazolyl.
  • R 1 is unsubstituted imidazolyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted isoxazolyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted oxazolyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridinyl.
  • R 1 is unsubstituted thiazolyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyrimidinyl. In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is unsubstituted pyridazinyl.
  • R 1 is selected from In some embodiments of a compound of Formula (III) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is in some embodiments, R 1 is selected from wherein each is optinally substituted with 1, 2 or 3 R 15a . In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is In some embodiments, R 1 is
  • described herein is a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is selected from a compound of Table 1A:
  • R 2 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N
  • R 1 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R
  • R 2b and R 3b are taken together to form a C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1- 9 heteroaryl; wherein C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, three, or four groups selected from R 15e ;
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O)
  • each R 10 is independently hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 12 is independently hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 13 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • R 2 is C 6-10 aryl or C 1-
  • R 2 is C 1-9 heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is 5-or 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is pyridinyl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is phenyl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is
  • Z 1 is CR 1b ;
  • Z 2 is CR 2b ;
  • Z 3 is CR 3b .
  • Z 2 is CR 2b ;
  • Z 3 is CR 3b .
  • Z 1 is CR 1b ;
  • Z 2 is N
  • Z 3 is CR 3b .
  • Z 1 is CR 1b ;
  • Z 2 is CR 2b ;
  • R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) , wherein C 1-6 alkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from R 15b .
  • R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 1-6 alkyl, C 3-6 cycloalkyl, and C 2-9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from R 15b .
  • R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 3-6 cycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 3-6 cycloalkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • R 1b , R 2b , and R 3b are independently hydrogen, halogen, -OR 10 , -SR 10 , or -SF 5 .
  • R 1b , R 2b , and R 3b are independently hydrogen or -OR 10 .
  • R 1b , R 2b , and R 3b are hydrogen.
  • R 1b is hydrogen
  • R 2b and R 3b are taken together to form a C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; wherein C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, three, or four groups selected from R 15e .
  • R 2b and R 3b are taken together to form C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; wherein C 3-6 cycloalkyl and C 2-9 heterocycloalkyl are optionally substituted with one, two, three, or four groups selected from R 15e .
  • R 2b and R 3b are taken together to form C 2-9 heterocycloalkyl optionally substituted with one, two, three, or four groups selected from R 15e .
  • R 2b and R 3b are taken together to form C 2-6 heterocycloalkyl optionally substituted with one, two, three, or four groups selected from R 15e .
  • R 2b and R 3b are taken together to form C 6-9 heterocycloalkyl optionally substituted with one, two, three, or four groups selected from R 15e .
  • R 2b and R 3b are taken together to form a 5-to 7-membered heterocycloalkyl containing one or two heteroatoms selected from O and N. In some embodiments of a compound of Formula (IV) , R 2b and R 3b are taken together to form a 6-membered heterocycloalkyl containing one heteroatom that is O.
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, or C 1-6 haloalkyl.
  • each R 15e are independently halogen, oxo, C 1-6 alkyl, or C 1-6 haloalkyl.
  • two R 15e on the adjacent carbon are taken together to form a C 2 alkenylene.
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; each optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1- 6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl.
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; each optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1- 6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl.
  • R 2b and R 3b are taken together to form
  • R 1 is C 6-10 aryl or C 1- 9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is 5-or 6-membered heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is 5-membered heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is optionally substituted C 1-9 heteroaryl. In some embodiments of a compound of Formula (IV) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (IV) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 membered heteroaryl. In some embodiments of a compound of Formula (IV) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 6 membered heteroaryl.
  • R 1 is monocyclic heteroaryl. In some embodiments of a compound of Formula (IV) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is bicyclic heteroaryl. In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from R 15a . In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxyl.
  • R 1 is optionally substituted with one, two, or three groups selected from oxo, -CN, amino, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl and thiazolyl, wherein pyrazolyl and thiazolyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is thiazolyl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is pyrazolyl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a , each R 15b , and each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a , each R 15b , and each R 15c are independently -OR 10 .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a are independently C 1-6 alkyl, C 3- 10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15a are independently -OR 10 .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15b are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15b are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15b are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15b are independently C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15b are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15b are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15b are independently -OR 10 .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15c are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15c are independently C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (IV) , each R 15c are independently -OR 10 .
  • R 2 is C 1-9 heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N
  • R 1 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • X is -C (R 6 ) (R 6a ) -, -S-, -O-, or -N (R 7 ) -;
  • R 6 and R 6a are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C (O
  • R 6 and R 6a are taken together to form an oxo
  • R 7 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • Ring A is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl;
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O)
  • n 0-6;
  • each R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 12 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 13 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • R 2 is 5-or 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is pyridinyl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is
  • Ring A is C 3-6 cycloalkyl or C 2- 9 heterocycloalkyl.
  • Ring A is C 2-9 heterocycloalkyl.
  • Ring A is C 2-6 heterocycloalkyl.
  • Ring A is C 6-9 heterocycloalkyl. In some embodiments of a compound of Formula (V) , Ring A is 6-membered heterocycloalkyl. In some embodiments of a compound of Formula (V) , Ring A is 5-to 7-membered heterocycloalkyl containing one or two heteroatoms elected from O and N. In some embodiments of a compound of Formula (V) , Ring A is 6-membered heterocycloalkyl containing one heteroatom that is O.
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, or C 1-6 haloalkyl.
  • each R 15e are independently halogen, oxo, C 1-6 alkyl, or C 1-6 haloalkyl.
  • two R 15e on the adjacent carbon are taken together to form a C 2 alkenylene.
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; each optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1- 6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl.
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; each optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1- 6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl.
  • n is 0-4. In some embodiments of a compound of Formula (V) , n is 2-4. In some embodiments of a compound of Formula (V) , n is 2. In some embodiments of a compound of Formula (V) , n is 1 or 2. In some embodiments of a compound of Formula (V) , n is 1. In some embodiments of a compound of Formula (V) , n is 1-3.
  • Z 1 is N. In some embodiments of a compound of Formula (V) , Z 1 is CR 1b .
  • R 1b is hydrogen or halogen. In some embodiments of a compound of Formula (V) , R 1b is hydrogen.
  • X is -C (R 6 ) (R 6a ) -, -S-, or -O-. In some embodiments of a compound of Formula (V) , X is -C (R 6 ) (R 6a ) -or -O-. In some embodiments of a compound of Formula (V) , X is -C (R 6 ) (R 6a ) -. In some embodiments of a compound of Formula (V) , X is -O-. In some embodiments of a compound of Formula (V) , X is -S-.
  • X is -N (R 7 ) -. In some embodiments of a compound of Formula (V) , X is -S-, -O-, or -N (R 7 ) -.
  • R 6 and R 6a are independently hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl. In some embodiments of a compound of Formula (V) , R 6 and R 6a are independently hydrogen or C 1-6 alkyl. In some embodiments of a compound of Formula (V) , R 6 and R 6a are hydrogen. In some embodiments of a compound of Formula (V) , R 6 and R 6a are taken together to form an oxo.
  • R 7 is hydrogen, C 1-6 alkyl, or C 1- 6 haloalkyl. In some embodiments of a compound of Formula (V) , R 7 is hydrogen or C 1-6 alkyl. In some embodiments of a compound of Formula (V) , R 7 is hydrogen.
  • R 1 is C 6-10 aryl or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is 5-or 6-membered heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is 5-membered heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is optionally substituted C 1-9 heteroaryl. In some embodiments of a compound of Formula (V) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (V) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 membered heteroaryl. In some embodiments of a compound of Formula (V) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 6 membered heteroaryl.
  • R 1 is monocyclic heteroaryl. In some embodiments of a compound of Formula (V) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is bicyclic heteroaryl. In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from R 15a . In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxyl.
  • R 1 is optionally substituted with one, two, or three groups selected from oxo, -CN, amino, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl and thiazolyl, wherein pyrazolyl and thiazolyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is thiazolyl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is pyrazolyl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is In some embodiments of a compound of Formula (V) , R 1 is
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a , each R 15b , and each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a , each R 15b , and each R 15c are independently -OR 10 .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a are independently halogen, C 1-6 alkyl, C 1- 6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a are independently C 1-6 alkyl, C 3- 10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15a are independently -OR 10 .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15b are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15b are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15b are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15b are independently C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15b are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15b are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15b are independently -OR 10 .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15c are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15c are independently C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (V) , each R 15c are independently -OR 10 .
  • R 2 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N
  • R 1 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • X is -C (R 6 ) (R 6a ) -, -S-, -O-, or -N (R 7 ) -;
  • R 6 and R 6a are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C (O
  • R 6 and R 6a are taken together to form an oxo
  • R 7 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • Ring B is C 3-6 cycloalkyl, C 6-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl;
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O)
  • n 0-6;
  • each R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 12 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 13 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • R 2 is C 6-10 aryl or C 1- 9 heteroaryl; each optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is C 1-9 heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is 5-or 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is pyridinyl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is phenyl optionally substituted with one, two, three, or four groups selected from R 15c .
  • R 2 is
  • Ring B is C 6-9 heterocycloalkyl.
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, or C 1-6 haloalkyl.
  • each R 15e are independently halogen, oxo, C 1-6 alkyl, or C 1-6 haloalkyl.
  • two R 15e on the adjacent carbon are taken together to form a C 2 alkenylene.
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; each optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1- 6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl.
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; each optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1- 6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl.
  • n is 0-4. In some embodiments of a compound of Formula (VI) , n is 2-4. In some embodiments of a compound of Formula (VI) , n is 2. In some embodiments of a compound of Formula (VI) , n is 1 or 2. In some embodiments of a compound of Formula (VI) , n is 1. In some embodiments of a compound of Formula (VI) , n is 1-3.
  • Z 1 is N. In some embodiments of a compound of Formula (VI) , Z 1 is CR 1b .
  • R 1b is hydrogen or halogen. In some embodiments of a compound of Formula (VI) , R 1b is hydrogen.
  • X is -C (R 6 ) (R 6a ) -, -S-, or -O-. In some embodiments of a compound of Formula (VI) , X is -C (R 6 ) (R 6a ) -or -O-. In some embodiments of a compound of Formula (VI) , X is -C (R 6 ) (R 6a ) -. In some embodiments of a compound of Formula (VI) , X is -O-. In some embodiments of a compound of Formula (VI) , X is -S-.
  • X is -N (R 7 ) -. In some embodiments of a compound of Formula (VI) , X is -S-, -O-, or -N (R 7 ) -.
  • R 6 and R 6a are independently hydrogen, halogen, C 1-6 alkyl, or C 1-6 haloalkyl. In some embodiments of a compound of Formula (VI) , R 6 and R 6a are independently hydrogen or C 1-6 alkyl. In some embodiments of a compound of Formula (VI) , R 6 and R 6a are hydrogen. In some embodiments of a compound of Formula (VI) , R 6 and R 6a are taken together to form an oxo.
  • R 7 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl. In some embodiments of a compound of Formula (VI) , R 7 is hydrogen or C 1- 6 alkyl. In some embodiments of a compound of Formula (VI) , R 7 is hydrogen.
  • R 1 is C 6-10 aryl or C 1- 9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is 5-or 6-membered heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is 5-membered heteroaryl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is optionally substituted C 1-9 heteroaryl. In some embodiments of a compound of Formula (VI) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 or 6 membered heteroaryl. In some embodiments of a compound of Formula (VI) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 5 membered heteroaryl. In some embodiments of a compound of Formula (VI) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is optionally substituted 6 membered heteroaryl.
  • R 1 is monocyclic heteroaryl. In some embodiments of a compound of Formula (VI) , or a pharmaceutically acceptable salt or solvate thereof, R 1 is bicyclic heteroaryl. In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from R 15a . In some embodiments, R 1 is optionally substituted with one, two, or three groups selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxyl.
  • R 1 is optionally substituted with one, two, or three groups selected from oxo, -CN, amino, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl.
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one, two, or three groups selected from R 15a and each R 15a is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1- 9 heteroaryl selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl are substituted with one group selected from R 15a and R 15a is selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and -OR 10 .
  • R 1 is C 1-9 heteroaryl selected from pyrazolyl and thiazolyl, wherein pyrazolyl and thiazolyl are optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is thiazolyl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is pyrazolyl optionally substituted with one, two, or three groups selected from R 15a .
  • R 1 is In some embodiments of a compound of Formula (VI) , R 1 is
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1- 9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 .
  • each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a , each R 15b , and each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a , each R 15b , and each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a , each R 15b , and each R 15c are independently -OR 10 .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15a are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15a are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a are independently C 1-6 alkyl, C 3- 10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15a are independently -OR 10 .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15b are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15b are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15b are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15b are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15b are independently C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15b are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15b are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15b are independently -OR 10 .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1- 9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, -OR 10 , or -N (R 10 ) (R 11 ) .
  • each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15c are independently halogen, C 1-6 alkyl, C 1-6 haloalkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15c are independently halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15c are independently halogen, C 1-6 alkyl, or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15c are independently C 1- 6 alkyl, C 3-10 cycloalkyl, or -OR 10 .
  • each R 15c are independently C 1-6 alkyl or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15c are independently C 3-10 cycloalkyl or -OR 10 . In some embodiments of a compound of Formula (VI) , each R 15c are independently -OR 10 .
  • each R 10 is independently hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1- 9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • each R 10 is independently hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, wherein C 1-6 alkyl, C 3-6 cycloalkyl, and C 2-9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • each R 10 is independently hydrogen, C 1-6 alkyl, or C 1- 6 haloalkyl, wherein C 1-6 alkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • each R 10 is independently hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 10 is independently C 1- 6 alkyl or C 1-6 haloalkyl. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 10 is independently C 1-6 alkyl. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 10 is methyl. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 10 is independently C 1-6 haloalkyl.
  • each R 11 is independently hydrogen or C 1-6 alkyl. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 11 is independently hydrogen. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 11 is independently C 1-6 alkyl. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 12 is independently hydrogen, C 1-6 alkyl, or C 1- 6 haloalkyl.
  • each R 12 is independently hydrogen or C 1-6 alkyl. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 12 is independently hydrogen. In some embodiments of a compound of Formula (IV) , (V) , or (VI) , each R 12 is independently C 1-6 alkyl.
  • each R 13 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1- 6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • each R 13 is independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1- 6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • each R 13 is independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, or C 2-9 heterocycloalkyl, wherein C 1-6 alkyl, C 3-6 cycloalkyl, and C 2- 9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • each R 13 is independently hydrogen, C 1-6 alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1- 6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • each R 13 is independently hydrogen or C 1-6 alkyl.
  • each R 13 is independently C 1-6 alkyl.
  • described herein is a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is selected from a compound of Table 1B:
  • described herein is a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is selected from a compound of Table 1C:
  • disclosure provided herein is further illustrated in numbered embodiments as the following.
  • Embodiment 1 A compound of Formula (IV) , or a pharmaceutically acceptable salt thereof:
  • R 2 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N
  • Z 2 is CR 2b or N
  • Z 3 is CR 3b or N
  • R 1 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R
  • R 2b and R 3b are taken together to form a C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1- 9 heteroaryl; wherein C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, three, or four groups selected from R 15e ;
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O)
  • each R 10 is independently hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is independently hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 12 is independently hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 13 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • Embodiment 2 The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein R 2 is C 6-10 aryl or C 1-9 heteroaryl; each optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 3 The compound of embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 2 is C 1-9 heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 4 The compound of embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 2 is 5-or 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 5 The compound of embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 2 is 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 6 The compound of embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 2 is pyridinyl optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 7 The compound of embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 2 is phenyl optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 8 The compound of any one of embodiments 1-7, or a pharmaceutically
  • Z 2 is CR 2b ;
  • Z 3 is CR 3b .
  • Embodiment 9 The compound of any one of embodiments 1-7, or a pharmaceutically acceptable salt thereof, wherein:
  • Z 1 is CR 1b ;
  • Z 2 is N
  • Z 3 is CR 3b .
  • Embodiment 10 The compound of any one of embodiments 1-7, or a pharmaceutically acceptable salt thereof, wherein:
  • Z 1 is CR 1b ;
  • Z 2 is CR 2b ;
  • Embodiment 11 The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, wherein R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) , wherein C 1- 6 alkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from R 15b .
  • Embodiment 12 The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, wherein R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 1-6 alkyl, C 3-6 cycloalkyl, and C 2-9 heterocycloalkyl are optionally substituted with one, two, or three groups selected from R 15b .
  • R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 1-6 alkyl, C 3-6 cycloalkyl, and
  • Embodiment 13 The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, wherein R 1b , R 2b , and R 3b are independently hydrogen, halogen, C 3-6 cycloalkyl, -OR 10 , -SR 10 , or -SF 5 , wherein C 3-6 cycloalkyl is optionally substituted with one, two, or three groups selected from R 15b .
  • Embodiment 14 The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, wherein R 1b , R 2b , and R 3b are independently hydrogen, halogen, -OR 10 , -SR 10 , or -SF 5 .
  • Embodiment 15 The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, wherein R 1b , R 2b , and R 3b are independently hydrogen or -OR 10 .
  • Embodiment 16 The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, wherein R 1b , R 2b , and R 3b are hydrogen.
  • Embodiment 17 A compound of Formula (V) , or a pharmaceutically acceptable salt thereof:
  • R 2 is C 1-9 heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N
  • R 1 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, or three groups selected from R 15a ;
  • R 1b is hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF 5 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C
  • X is -C (R 6 ) (R 6a ) -, -S-, -O-, or -N (R 7 ) -;
  • R 6 and R 6a are independently hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O) 2 R 13 , -C (O) R 13 , -S (O) R 13 , -OC (O) R 13 , -C (O) N (R 10 ) (R 11 ) , -C (O) C (O
  • R 6 and R 6a are taken together to form an oxo
  • R 7 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • Ring A is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl;
  • each R 15a , each R 15b , and each R 15c are independently halogen, oxo, -CN, C 1-6 alkyl, C 1- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13
  • each R 15e are independently halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2- 9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -SR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -OC (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) N (R 10 ) (R 11 ) , -N (R 12 ) C (O) OR 13 , -N (R 12 ) S (O)
  • n 0-6;
  • each R 10 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl;
  • each R 11 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 12 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl
  • each R 13 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2- 9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3- 6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, and C 1-9 heteroaryl.
  • Embodiment 18 The compound of embodiment 17, or a pharmaceutically acceptable salt thereof, wherein R 2 is 5-or 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 19 The compound of embodiment 17, or a pharmaceutically acceptable salt thereof, wherein R 2 is 6-membered heteroaryl optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 20 The compound of embodiment 17, or a pharmaceutically acceptable salt thereof, wherein R 2 is pyridinyl optionally substituted with one, two, three, or four groups selected from R 15c .
  • Embodiment 21 The compound of any one of embodiments 17-20, or a pharmaceutically acceptable salt thereof, wherein Ring A is C 3-6 cycloalkyl or C 2-9 heterocycloalkyl.
  • Embodiment 22 The compound of any one of embodiments 17-20, or a pharmaceutically acceptable salt thereof, wherein Ring A is C 2-9 heterocycloalkyl.
  • Embodiment 23 The compound of any one of embodiments 17-20, or a pharmaceutically acceptable salt thereof, wherein Ring A is C 2-6 heterocycloalkyl.
  • Embodiment 24 The compound of any one of embodiments 17-20, or a pharmaceutically acceptable salt thereof, wherein Ring A is C 6-9 heterocycloalkyl.
  • Embodiment 25 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein each R 15e are independently halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6-10 aryl, -CH 2 -C 6-10 aryl, C 1-9 heteroaryl, -CH 2 -C 1-9 heteroaryl, -OR 10 , -N (R 10 ) (R 11 ) , -C (O) OR 10 , -C (O) R 13 , or -C (O) N (R 10 ) (R 11 ) .
  • each R 15e are independently halogen, oxo, -CN, C 1- 6 alkyl, C 1-6 haloalkyl,
  • Embodiment 26 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein each R 15e are independently halogen, oxo, -CN, C 1- 6 alkyl, or C 1-6 haloalkyl.
  • Embodiment 27 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein each R 15e are independently halogen, oxo, C 1-6 alkyl, or C 1-6 haloalkyl.
  • Embodiment 28 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein two R 15e on the adjacent carbon are taken together to form a C 2 alkenylene.
  • Embodiment 29 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; each optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1- 6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • Embodiment 30 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • Embodiment 31 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein two R 15e on the same atom are taken together to form a C 3-6 cycloalkyl.
  • Embodiment 32 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl or C 2-9 heterocycloalkyl; each optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1- 6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • Embodiment 33 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, -OR 10 , and -N (R 10 ) (R 11 ) .
  • Embodiment 34 The compound of any one of embodiments 17-24, or a pharmaceutically acceptable salt thereof, wherein two R 15e on the different atom are taken together to form a C 3-6 cycloalkyl.
  • Embodiment 35 The compound of any one of embodiments 17-34, or a pharmaceutically acceptable salt thereof, wherein n is 0-4.
  • Embodiment 36 The compound of any one of embodiments 17-35, or a pharmaceutically acceptable salt thereof, wherein n is 2-4.
  • Embodiment 37 The compound of any one of embodiments 17-36, or a pharmaceutically acceptable salt thereof, wherein n is 2.
  • Embodiment 38 The compound of any one of embodiments 17-20, or a pharmaceutically acceptable salt thereof, wherein is
  • Embodiment 39 A compound of Formula (VI) , or a pharmaceutically acceptable salt thereof:
  • R 2 is C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, or C 1-9 heteroaryl; each optionally substituted with one, two, three, or four groups selected from R 15c ;
  • Z 1 is CR 1b or N

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AU2022390319A AU2022390319A1 (en) 2021-11-16 2022-11-15 Lysine acetyltransferase 6a (kat6a) inhibitors and uses thereof
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EP22894767.7A EP4433474A4 (en) 2021-11-16 2022-11-15 LYSINE ACETYLTRANSFERASE 6A (KAT6A) INHIBITORS AND THEIR USES
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