EP4355751A1 - Composés hétéroaryle fusionnés utiles en tant qu'agents anticancéreux - Google Patents

Composés hétéroaryle fusionnés utiles en tant qu'agents anticancéreux

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Publication number
EP4355751A1
EP4355751A1 EP22740705.3A EP22740705A EP4355751A1 EP 4355751 A1 EP4355751 A1 EP 4355751A1 EP 22740705 A EP22740705 A EP 22740705A EP 4355751 A1 EP4355751 A1 EP 4355751A1
Authority
EP
European Patent Office
Prior art keywords
optionally substituted
alkyl
ioaryl
compound
pharmaceutically acceptable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP22740705.3A
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German (de)
English (en)
Inventor
Liansheng Li
Xiuwen Zhu
Pingda Ren
Yi Liu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kumquat Biosciences Inc
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Kumquat Biosciences Inc
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Filing date
Publication date
Application filed by Kumquat Biosciences Inc filed Critical Kumquat Biosciences Inc
Publication of EP4355751A1 publication Critical patent/EP4355751A1/fr
Pending legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • Cancer e.g., tumor, neoplasm, metastases
  • K-Ras Kirsten Ras oncogene
  • PD AC pancreatic ductal adenocarcinoma
  • Ras proteins have long been considered to be “undruggable,” due to, in part, high affinity to their substrate Guanosine-5'-triphosphate (GTP) and/or their smooth surfaces without any obvious targeting region.
  • GTP Guanosine-5'-triphosphate
  • Recently, a specific G12C Ras gene mutation has been identified as a potential draggable target.
  • such therapeutic approach is still limiting, as the G12C mutation in Ras has a low prevalence rate (e.g., about 3% in PD AC) as compared to other known Ras mutations.
  • compositions and methods can be particularly useful for treating a variety of the diseases including, but not limited to, cancers and neoplasia conditions.
  • the present disclosure addresses these needs, and provides additional advantages applicable for diagnosis, prognosis, and treatment for a wide diversity of diseases.
  • W is C(O), S(O), or S(0) 2 ;
  • V is C(R 17 ) and J is C(R 16 ), or V is C(R 17 ) and J is N, or J is C(R 17 ) and V is C(R 16 ), or J is C(R 17 ) and V is N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, - N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, Ci-C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl, wherein Ci-Cealkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl, are optionally substituted with one, two, or three R 20a ; R 7 is a 3-12 membered nitrogen containing heterocycloalkyl or 5-12 membered nitrogen containing heteroaryl, wherein the 3-12 membered nitrogen containing heterocyclo
  • R 4 is optionally an electrophilic moiety capable of forming a covalent bond with a cysteine, serine, or aspartate residue at an amino acid position corresponding to 12 or 13 of a human KRAS protein), wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R 20a ;
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, Ci-Cealkyl, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, - S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, -N(R 14 )C(0)0-, and - N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci- 9 heteroaryl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0) 2 R 15 , -
  • R 17 is -lA-R 19 ;
  • L 1 is selected from a bond, Ci-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, -
  • ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 201 ; or R lf and R lg are joined to form a 4-7 membered heterocycloalkyl ring or a 4-7 membered cycloalkyl ring, wherein the 4-7 membered heterocycloalkyl ring or 4-7 membered cycloalkyl ring are optionally substituted with one, two, or three R 201 ;
  • R lc is selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, and Ci-9heteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R 201 R 19 is selected from a C3-i2cycloalkyl (e.g., monocyclic, bicyclic, or polycyclic), C2-iiheterocycloalkyl (e.g., monocyclic, bicyclic, or polycyclic), C6-i2aryl (e.g., monocyclic, bicyclic, or polycyclic), and C2-i2heteroaryl (e
  • R 16 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0)
  • Ci- 6alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 20d ;
  • R 12a is selected from Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH2-Ci-9heteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -G5-ioaryl, -CH 2 -Ci-9heteroaryl, and Ci-dictcro
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -CH 2 -C3-iocycloalkyl, C 2. gheterocycloalkyl, -CH 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -Ci-9heteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -CH 2 -C3-iocycloalkyl, C 2 -9heterocycloalkyl, -CH 2 - C 2 -9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, Ce-ioaryl, Ci- 9 heteroaiyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0) 2 R
  • each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, -CH 2 -C3-
  • gheterocycloalkyl, -CH 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -Ci-9heteroaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- 6 alkyl, Ci-ehaloalkyl, Ci- 6 alkoxy, Ci- 6 haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(0)0R 22 , -C(0)N(R 22 )(R 23 ), - C(0)C(0)N(R 22 )(R 23 ), -0C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)0
  • each R 22 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- siheterocycloalkyl, C 6 -ioaryl, and Ci-dictcroaryl: each R 23 is independently selected from H and Ci- 6 alkyl; each R 24 is independently selected from H and Ci- 6 alkyl; each R 25 is independently selected from Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, Ce- ioaryl, and Ci-gheteroaryl; and indicates a single or double bond such that all valences are satisfied.
  • X is C(R 3 ). In embodiments, X is N. In embodiments, J is C(R 16 ) and V is C(R 17 ). In embodiments, W is C(O).
  • the compound, or a pharmaceutically acceptable salt or solvate thereof has the structure: , , , Formula (IA12). [0008] In embodiments, the compound, or a pharmaceutically acceptable salt or solvate thereof, has the structure:
  • the compound, or a pharmaceutically acceptable salt or solvate thereof has the structure:
  • L 7 is a bond. [0011] In embodiments, L 7 is -NH-.
  • R 7 is a 3-12 membered nitrogen containing heterocycloalkyl, wherein the 3-12 membered nitrogen containing heterocycloalkyl is optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; and wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i 2 cycloalkyl, Ci- li heterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl, wherein the C3-i 2 cycloalkyl, Ci-nheterocycloalkyl, C 6 -i 2 aryl, or Ci- nheteroaryl are optionally substituted with one, two, or three R 20a .
  • R 16 is independently selected from hydrogen and halogen. In embodiments, R 16 is independently selected from hydrogen and fluoro.
  • R 8 is selected from Ci- 6 alkyl, C3-iocycloalkyl, and C2-s > heterocycloalkyl, wherein Ci- 6 alkyl, C3-iocycloalkyl, and C2-s > heterocycloalkyl are optionally substituted with one, two, or three R 20c independently selected from halogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, and C2-9heterocycloalkyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, and oxetanyl, wherein said methyl, cyclopropyl, cyclobutyl, and oxetanyl are optionally substituted with one, two, or three R 20c independently selected from fluoro, methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 3 is hydrogen or CN.
  • L 1 is a bond.
  • L 1 is selected from a Ci-Cealkyl, C2-C6alkenyl, C2- Cealkynyl, -C(O)-, -NHC(O)-, -C(0)NH-, CH 2 0, CH 2 NH, and CH 2 .
  • R 19 is a monocyclic ring. In embodiments, R 19 is a bicyclic ring system. In embodiments, R 19 is a polycyclic ring system.
  • Q 1 , Q 3 , and Q 5 are independently N or C(R ld );
  • Q 4 and Q 6 are independently O, S, C(R la )(R lb ), or N(R lc );
  • X 4 , X 5 , X 6 , X 9 , X 10 , X 11 , X 12 , and X 16 are independently selected from C(R la ) or N;
  • X 7 and X 8 are independently selected from C(R la ), C(R la )(R lb ), N, or N(R lc );
  • X 13 is selected from a bond, C(O), C(R la )(R lb ), C(0)C(R la )(R lb ), C(R la )(R lb )C(R la )(R lb ), C(R la )(R lb )N(R lc ), and N(R lc );
  • X 14 and X 15 are independently selected from a bond, C(O), C(R la )(R lb ), and N(R lc ); each R la , R lb , R ld , R lf , R lg , and R lh are each independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci-dictcroarvl.
  • C 6 -ioaryl, and Cj-dictcroaryl are optionally substituted with one, two, or three R 201 ; or R la and R lb bonded to the same carbon are joined to form a 3-10 membered heterocycloalkyl ring or a C3-iocycloalkyl ring, wherein the 3-10 membered heterocycloalkyl ring or C3-iocycloalkyl ring are optionally substituted with one, two, or three R 201 ; or two R la bonded to adjacent atoms are joined to form a 3-10 membered heterocycloalkyl ring, a C 6 -ioaryl ring, a 5-12 membered heteroaryl ring, or a C3-iocycloalkyl ring, wherein the 3-10 membered heterocycloalkyl ring, C 6 -ioaryl ring, 5-12 membered heteroaryl ring, or C3-iocycloalkyl ring
  • C 6 -ioaryl, and Cj-dictcroaryl are optionally substituted with one, two, or three R 201 .
  • each L 2 is independently a bond.
  • each R 5 is independently selected from:
  • R 4 is independently -C(0)R 15 .
  • R 4 is independently -C(0)R 15 and the R 15 is independently selected from C 2-6 alkenyl, C 2-6 alkynyl, C 2 -9heterocycloalkyl, and CiActcroaryl. wherein C 2. 6 alkenyl, C 2-6 alkynyl, C 2 -9heterocycloalkyl, and CiAeteroaryl are optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and the R 15 is independently C 2-6 alkenyl, wherein C 2-6 alkenyl is optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and the R 15 is independently C 2 -9heterocycloalkyl, wherein C 2 -9heterocycloalkyl is optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and the R 15 is independently CiAeteroaryl, wherein Ci- gheteroaryl is optionally substituted with one, two, or three R 20f .
  • R 4 is an electrophilic moiety capable of forming a covalent bond with a cysteine, serine, or aspartate residue at an amino acid position corresponding to 12 or 13 of a human KRAS protein.
  • A is a monovalent form of a compound described herein;
  • L AB is a covalent linker bonded to A and B; and
  • B is a monovalent form of a degradation enhancer.
  • the degradation enhancer is capable of binding a protein selected from E3A, mdm2, APC, EDD1, SOCS/BC-box/eloBC/CUL5/RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP 12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von-Hippel-
  • ubiquitin ligase XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBX04, FBX031, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadomide, iberdomide, and CC-885.
  • the compound of claim 74 wherein the degradation enhancer is capable of binding a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE20, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1.
  • a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, U
  • L AB is -L AB1 -L AB2 -L AB3 -L AB4 -L AB5 -; L AB I . IT 02 .
  • L ab ⁇ L AB and L ABS are independently a bond, -O-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, - N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, Ci- 6 alkylene, (-0-Ci- 6 alkyl) z -, (-Ci- 6 alkyl-0) z -, C 2-6 alkenylene, C 2-6 alkynylene, Ci- 6 haloalky
  • narylene, or Ci-nheteroarylene are optionally substituted with one, two, or three R 20j ; wherein each Ci- 6 alkyl of (-0-Ci- 6 alkyl) z - and (-Ci- 6 alkyl-0) z - is optionally substituted with one, two, or three R 20j ; z is independently an integer from 0 to 10; each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, G- 6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 - Ci-9heteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alky
  • Ci-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy, Ci- 6 haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), - C(0)0R 22 , -C(0)N(R 22 )(R 23 ), -C(0)C(0)N(R 22 )(R 23 ), -0C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)N(R 22 )
  • L AB is -(0-C 2 alkyl) z - and z is an integer from 1 to 10. In embodiments, L AB is -(C 2 alkyl-0-) z - and z is an integer from 1 to 10. In embodiments, L AB is -(CH 2 ) Z IL AB2 (CH 2 0) Z2 -, wherein L Ali2 is a bond, a 5 or 6 membered heterocycloalkylene or heteroarylene, phenylene, -(C2-
  • L AB is -(CH 2 ) zi (CH 2 0) z2 -, wherein zl and z2 are each independently an integer from 0 to 10.
  • L AB is a PEG linker.
  • B is a monovalent form of a compound selected from
  • a pharmaceutical composition comprising a compound described herein or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.
  • a method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.
  • a method of modulating activity of a Ras protein comprising contacting a Ras protein with an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the activity of the Ras protein.
  • the method includes administering an additional agent or therapy.
  • a method of inhibiting cell growth comprising administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, to a cell expressing a Ras protein, thereby inhibiting growth of said cells.
  • the method includes administering an additional agent to said cell.
  • the additional agent comprises (1) an inhibitor of MEK; (2) an inhibitor of epidermal growth factor receptor (EGFR) and/or of mutants thereof; (3) an immunotherapeutic agent; (4) a taxane; (5) an anti-metabolite; (6) an inhibitor of FGFR1 and/or FGFR2 and/or FGFR3 and/or of mutants thereof; (7) a mitotic kinase inhibitor; (8) an anti-angiogenic drag; (9) a topoisomerase inhibitor; (10) a platinum-containing compound; (12) an inhibitor of c-MET and/or of mutants thereof; (13) an inhibitor of BCR-ABL and/or of mutants thereof; (14) an inhibitor of ErbB2 (Her2) and/or of mutants thereof; (15) an inhibitor of AXL and/or of mutants thereof; (16) an inhibitor of NTRK1 and/or of mutants thereof; (17) an inhibitor of RET and/or of mutants thereof; (18) an inhibitor of A-Raf and or
  • the additional agent comprises an inhibitor of SHP2 selected from RMC-4630, TN0155, JAB-3068, IACS-13909/BBP-398, SHP099, ERAS-601, and RMC-4550.
  • the additional agent comprises an inhibitor of SOS selected from RMC-5845, BI-3406, BI-1701963, MRTX0902, and BAY 293.
  • the additional agent comprises an inhibitor of EGFR selected from afatinib, erlotinib, gefitinib, lapatinib, cetuximab panitumumab, osimertinib, olmutinib, and EGF-816.
  • the additional agent comprises an inhibitor of MEK selected from trametinib, cobimetinib, binimetinib, selumetinib, refametinib, and AZD6244.
  • the additional agent comprises an inhibitor of ERK selected from ulixertinib, MK-8353, LTT462, AZD0364, SCH772984, BIX02189, LY3214996, and ravoxertinib.
  • the additional agent comprises an inhibitor of CDK4/6 selected from palbociclib, ribociclib, and abemaciclib.
  • the additional agent comprises an inhibitor of BRAF selected from sorafenib, vemurafenib, dabrafenib, encorafenib, regorafenib, and GDC-879.
  • W is C(O), S(O), or S(0) 2 ;
  • V is C(R 17 ) and J is C(R 16 ), or V is C(R 17 ) and J is N, or J is C(R 17 ) and V is C(R 16 ), or J is C(R 17 ) and V is N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • R 7 is a 3-12 membered nitrogen containing heterocycloalkyl or 5-12 membered nitrogen containing heteroaryl, wherein the 3-12 membered nitrogen containing heterocycloalkyl or 5-12 membered nitrogen containing heteroaryl are optionally substituted with one or more R 1 , one or more R 4 , or one or more R 6 ; wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i2cycloalkyl, Ci-nheterocycloalkyl, C6-i2aryl, or Ci-nheteroaryl, wherein the C3-i2cycloalkyl, Ci-nheterocycloalkyl, C6-i2aryl, or Ci-nheteroaryl are optionally substituted with one, two, or three R 20a ; each R 1 is independently selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, Ci-Cealkyl, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, - S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, - N(R 14 )C(0)0-, and -N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0) 2 R
  • R 17 is -LkR 19 ;
  • L 1 is selected from a bond, Ci-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc ), and C(R
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), - C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , - S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )
  • R lc is selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, G,. ioaryl, and Ci-dictcroaiyl. wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 201
  • R 19 is selected from a C3-i2cycloalkyl, C2-nheterocycloalkyl, C6-i2aryl, and C2-i2heteroaryl, wherein the G- ncycloalkyl, C2-iiheterocycloalkyl, C6-i2aryl, and C2-i2heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, G- 6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , - 0C(0)N(R 12 )(R 13
  • R 16 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, G- gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0)
  • R 12a is selected from Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C2- gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH2-Ci-9heteroaryl, and Ci- gheteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C2- gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH2-Ci-9heteroaryl, and Ci-
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C2- gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CEC-Ci-gheteroaryl, and Ci- gheteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C2- gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CEC-Ci-ghetero
  • X is C(R 3 ) or N; R 3 is selected from hydrogen, halogen, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2 - gheterocycloalkyl, C 6 -ioaryl, Ci-yhctcroan l.
  • each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -C 1 - gheteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C
  • Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 20f ; each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , and R 201 are each independently selected from halogen, -CN, Ci- 6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2 - gheterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl,
  • X is C(R 3 ). In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, X is N. [0040] In further embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof,
  • V is C(R 16 ) and J is C(R 17 ). In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, V is N and J is C(R 17 ). In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, J is N and V is C(R 17 ). In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, J is C(R 16 ) and V is C(R 17 ). In lurther embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, W is C(O). In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, W is S(O). In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, W is S(0) 2 .
  • the compound has the structure:
  • the compound has the structure: ), , 12).
  • L 7 is a bond. In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, L 7 is -NH-.
  • R 7 is a 3-12 membered nitrogen containing heterocycloalkyl, wherein the 3-12 membered nitrogen containing heterocycloalkyl is optionally substituted with one or more R 1 , one or more R 4 , or one or more R 6 ; and wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i2cycloalkyl, Ci-nheterocycloalkyl, C6-i2aryl, or Ci-nheteroaryl, wherein the C3-i2cycloalkyl, Ci- li heterocycloalkyl, C6-i2aryl, or Ci-nheteroaryl are optionally substituted with one, two, or three R 20a .
  • R 7 is
  • R 7 is integer from 0 to 12.
  • R 7 In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 7
  • R 16 is independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, and C3- 6 cycloalkyl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, and C3-6cycloalkyl are optionally substituted with one, two, or three R 20g .
  • R 16 is independently selected from hydrogen and halogen.
  • R 16 is independently selected from hydrogen and fluoro.
  • R 8 is selected from halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci- 9 heteroaiyl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)OR 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -OC(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ),
  • R 8 is selected from Ci- 6 alkyl, C3-iocycloalkyl, and C2-9heterocycloalkyl, wherein Ci- 6 alkyl, C3-iocycloalkyl, and C2- gheterocycloalkyl are optionally substituted with one, two, or three R 20c independently selected from halogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, and C2-9heterocycloalkyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, and oxetanyl, wherein said methyl, cyclopropyl, cyclobutyl, and oxetanyl are optionally substituted with one, two, or three R 20c independently selected from fluoro, methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 3 is hydrogen or CN. In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 3 is hydrogen.
  • L 1 is a bond. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, L 1 is selected from a Ci-C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, -C(O)-, -NHC(O)-, -C(0)NH-, CH 2 0, CH 2 NH, and CH 2 .
  • R 19 is a monocyclic ring. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 19 is a bicyclic ring system. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 19 is a polycyclic ring system. In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 19 is:
  • Q 1 , Q 3 , and Q 5 are independently N or C(R ld );
  • Q 4 and Q 6 are independently O, S, C(R la )(R lb ), or N(R lc );
  • X 4 , X 5 , X 6 , X 9 , X 10 , X 11 , and X 12 are independently selected from C(R la ) or N;
  • X 7 and X 8 are independently selected from C(R la ), C(R la )(R lb ), N, or N(R lc ); each R la , R lb , R ld , and R lh are each independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-dictcroaiyl.
  • Ci-dictcroaiyl wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2- dictcrocycloalkyl.
  • C 6 -ioaryl, and Cj-dictcroaryl are optionally substituted with one, two, or three R 201 .
  • R 2 is [0057] In further embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, each R 5 is independently selected from:
  • V is C(R 16 ) or N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • R 7 is a 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl are optionally substituted with one or more R 1 , one or more R 4 , or one or more R 6 ; two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i 2 cycloalkyl, Ci-nheterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl, wherein the C3- i 2 cycloalkyl.
  • Ci-nheterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl are optionally substituted with one, two, or three R 20a ; each R 1 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ci- 6 haloalkyl, C3- i 2 cycloalkyl.
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, G-Galkyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, - S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, - N(R 14 )C(0)0-, and -N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0) 2 R
  • R 17 is -G-R 19 ;
  • L 1 is selected from a bond, G-Galkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc ), and
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-dictcroarvl.
  • gheterocycloalkyl, C 6 -ioaryl, and Ci-dictcroarvl are optionally substituted with one, two, or three R 201 ; or R lf and R lg are joined to form a 4-7 membered heterocycloalkyl ring or a 4-7 membered cycloalkyl ring, wherein the 4-7 membered heterocycloalkyl ring or 4-7 membered cycloalkyl ring are optionally substituted with one, two, or three R 201 ;
  • R lc is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, CV,. ioaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 201
  • R 19 is selected from a C3-i 2 cycloalkyl, C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl, wherein the C3- i 2 cycloalkyl.
  • C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3- 6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , - 0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)
  • R 16 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0)
  • R 12a is selected from Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -CH 2 -C3-iocycloalkyl, C 2. gheterocycloalkyl, -CH 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -Ci-9heteroaryl, and Ci- yhctcroan l.
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -CH 2 -C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -Ci- 9 heteroaryl, and Ci- gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -CH 2 -C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl,
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2 - gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 ,
  • each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -C 1 - gheteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -io
  • Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 20f ; each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , and R 201 are each independently selected from halogen, -CN, Ci- 6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2 - gheterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl,
  • X is C(R 3 ). In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, X is N. [0060] In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, V is C(R 16 ). In further embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, V is N.
  • W is C(O). In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, W is S(O). In lurther embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, W is S(0) 2 .
  • the compound has the structure: , Formula Formula (IIA9), Formula (IIA10), Formula (IIA11), or Formula (IIA12).
  • L 7 is a bond. In further embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, L 7 is -NH-.
  • R 7 is a 3-12 membered heterocycloalkyl, wherein the 3-12 membered heterocycloalkyl is optionally substituted with one or more R 1 , one or more R 4 , or one or more R 6 ; and wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i2cycloalkyl, Ci- l i heterocycloalkyl, C6-i2aryl, or Ci-iiheteroaryl, wherein the C3-i2cycloalkyl, Ci-iiheterocycloalkyl, C6-i2aryl, or Ci- nheteroaryl are optionally substituted with one, two, or three R 20a .
  • p is an integer from 0 to 12;
  • X 2 is selected from N, C, C(R 6 ), C(R 4 ), CH, N(R'). N(R 4 ), N(R 6 ), O, S, S(O), C(H)(R 6 ), C(R 4 ) 2 , CH 2 , C(R 4 )(R 6 ),
  • X 3 is selected from N, C, C(R 6 ), and C(R 4 ).
  • R 7 In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 7
  • R 7 integer from 0 to 12.
  • R 7 In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 7
  • R 16 is independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, and C3-6cycloalkyl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, and C3-6cycloalkyl are optionally substituted with one, two, or three R 20g .
  • R 16 is independently selected from hydrogen and halogen.
  • R 16 is independently selected from hydrogen and fluoro.
  • R 8 is selected from halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci- 9 heteroaiyl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -C(0)C
  • R 8 is selected from Ci- 6 alkyl, C3-iocycloalkyl, and C2-9heterocycloalkyl, wherein Ci- 6 alkyl, C3-iocycloalkyl, and C2- gheterocycloalkyl are optionally substituted with one, two, or three R 20c independently selected from halogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, and C2-9heterocycloalkyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, and oxetanyl, wherein said methyl, cyclopropyl, cyclobutyl, and oxetanyl are optionally substituted with one, two, or three R 20c independently selected from fluoro, methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, oxetanylmethyl, and oxetanyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 3 is hydrogen or CN. In further embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 3 is hydrogen.
  • L 1 is a bond. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, L 1 is selected from a Ci-Cealkyl, C2-C6alkenyl, C2-Cealkynyl, -C(O)-, -NHC(O)-, -C(0)NH-, CH 2 0, CH 2 NH, and CH 2 .
  • R 19 is a monocyclic ring. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 19 is a bicyclic ring system. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 19 is a polycyclic ring system. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 19 is:
  • Q 1 , Q 3 , and Q 5 are independently N or C(R ld );
  • Q 4 and Q 6 are independently O, S, C(R la )(R lb ), or N(R lc );
  • X 4 , X 5 , X 6 , X 9 , X 10 , X 11 , and X 12 are independently selected from C(R la ) or N;
  • X 7 and X 8 are independently selected from C(R la ), C(R la )(R lb ), N, or N(R lc ); each R la , R lb , R ld , and R lh are each independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci-dictcroaiyl.
  • Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2- siheterocycloalkyl, C 6 -ioaryl, and Cj-dictcroaryl are optionally substituted with one, two, or three R 201 .
  • R 19 is: [0076] In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 2
  • each R 5 is independently selected from:
  • A is a monovalent form of a compound of Formula I, IA1, IA2, IA3, IA4, IA5, IA6, IA7, IA8, IA9, IA10, IA11, IA12, II, IIA1, IIA2, IIA3, IIA4, IIA5, IIA6, IIA7, IIA8, IIA9, IIA10, IIA11, IIA12, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, or XV;
  • L AB is a covalent linker bonded to A and B; and B is a monovalent form of a degradation enhancer.
  • the degradation enhancer is capable of binding a protein selected from E3A, mdm2, APC, EDD1, SOCS/BC-box/eloBC/CUL5/RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF 1, SMURF2, STUB1, TOPORS, TRIP 12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von-Hippel- Lindau ubiquitin ligase), WWP1, WWP2, Parkin, MK
  • the degradation enhancer is capable of binding a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE20, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1.
  • a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E
  • L AB is -L AB I -L AB1 -L AB, -L AB I -L AB5 -: independently a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, - )N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, Ci- 6 alkylene, (-0-Ci.
  • R 20e each are each independently selected from halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6c loalkyl, C 2 -9heterocycloalkyl, -CH 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, - CH 2 - roaiyl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(0)0R 22 , -C(0)N(R 22 )(R 23 ), - C(0) 0)N(R 22 )(R 23 ), -N(R 24 )C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)0R 25 , -N(R 24 )C(0)R 25 , -N(R 24 )S(0) 2 R 25 , -
  • ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -Ci-9heteroaryl, and GAeteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, -CN, CXalkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy, Ci- 6 haloalkoxy, -OR 21 , - SR 21 , -N(R 22 )(R 23 ), -C(0)0R 22 , -C(0)N(R 22 )(R 23 ), -C(0)C(0)N(R 22 )(R 23 ), -0C(0)N(R 22 )(R 23 ), - N(R 24 )C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)0R 25 , -N(R 24 )C(0)R 25 , -N(R 24 )S(0) 2 R 25 ,
  • each R 22 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2.
  • each R 23 is independently selected from H and Ci- 6 alkyl
  • each R 24 is independently selected from H and Ci- 6 alkyl
  • each R 25 is selected from Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, and G- gheteroaryl.
  • L AB is -(0-C 2 alkyl) z - and z is an integer from 1 to 10.
  • L AB is -(C 2 alkyl-0-) z - and z is an integer from 1 to 10.
  • L AB is -(CH 2 ) Z IL AB2 (CH 2 0) z2 -, wherein L Ali2 is a bond, a 5 or 6 membered heterocycloalkylene or heteroarylene, phenylene, -(C 2 -C4)alkynylene, -S0 2 - or -NH-; and zl and z2 are independently an integer from 0 to 10.
  • L AB is -(CH 2 ) Z I(CH 2 0) /2 -. wherein zl and z2 are each independently an integer from 0 to 10.
  • L AB is a PEG linker (e.g., divalent linker of 1 to 10 ethylene glycol subunits).
  • B is a monovalent form of a compound selected from
  • a pharmaceutical composition comprising a compound described herein (e.g., compound of Formula I, IA1, IA2, IA3, IA4, IA5, IA6, IA7, IA8, IA9, IA10, IA11, IA12, II, IIA1, IIA2, IIA3, IIA4, IIA5, IIA6, IIA7, IIA8, IIA9, IIA10, IIA11, IIA12, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, or XV; compound of Formula G, IF, I”, II”, 1-1, 1-G, 1-1”, I-G”, 1-3, 1-4, II- 1, XVI, XVII, XVIII, or XIX), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.
  • a compound described herein e.g., compound of Formula I, IA1, IA2, IA3, IA
  • a method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound described herein (e.g., compound of Formula I, IA1, IA2, 1 A3, IA4, IA5, IA6, IA7, IA8, IA9, IA10, IA11, IA12, II, IIA1, IIA2, IIA3, IIA4, IIA5, IIA6, IIA7, IIA8, IIA9, IIA10, II A 11, IIA12, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, or XV; compound of Formula F, IF, I”, II”, 1-1, 1-F, 1-1”, I-G”, 1-3, 1-4, II- 1, XVI, XVII, XVIII, or XIX), or a pharmaceutically acceptable salt or solvate thereof.
  • a compound described herein e.g., compound of Formula I, I
  • a method of modulating activity of a Ras comprising contacting a Ras protein with an effective amount of a compound described herein (e.g., compound of Formula I, IA1, IA2, 1 A3, IA4, IA5, IA6, IA7, IA8, IA9, IA10, IA11, IA12, II, IIA1, IIA2, IIA3, IIA4, IIA5, IIA6, IIA7, IIA8, IIA9, IIA10, IIA11, IIA12, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, or XV; compound of Formula F, IF, I”, II”, 1-1, 1-r, 1-1”, I-G”, 1-3, 1-4, II-l, XVI, XVII, XVIII, or XIX), or a pharmaceutically acceptable salt or solvate thereof
  • a compound described herein e.g., compound of Formula I, IA1,
  • the subject method comprises administering an additional agent or therapy.
  • a method of inhibiting cell growth comprising administering an effective amount of a compound described herein (e.g., compound of Formula I, IA1, IA2, IA3, IA4, IA5, IA6, IA7, IA8, IA9, IA10, IA11, IA12, II, IIA1, IIA2, IIA3, IIA4, IIA5, IIA6, IIA7, IIA8, IIA9, IIA10, IIA11, IIA12, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, or XV; compound of Formula F, IF, I”, II”, 1-1, 1-G, 1-1”, I-F”, 1-3, 1-4, II- 1, XVI, XVII, XVIII, or XIX), or a pharmaceutically acceptable salt or solvate thereof, to a cell expressing a Ras (e.g., K- Ras) protein,
  • a Ras e.g
  • a Ras (e.g., K-Ras) protein bound by a compound described herein e.g., compound of Formula I, IA1, IA2, IA3, IA4, IA5, IA6, IA7, IA8, IA9, IA10, IA11, IA12, II, IIA1, IIA2, IIA3, IIA4, IIA5, IIA6, IIA7, IIA8, IIA9, IIA10, IIA11, IIA12, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, or XV; compound of Formula F, IF, I”, II”, 1-1, 1-G, 1-1”, I-G”, 1-3, 1-4, II- 1, XVI, XVII, XVIII, or XIX), or a pharmaceutically acceptable salt or solvate thereof, wherein activity of said Ras (e.g., K-Ras) protein is
  • Standard techniques can be used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients.
  • Standard techniques can be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, lipofection). Reactions and purification techniques can be performed e.g., using kits of manufacturer's specifications or as commonly accomplished in the art or as described herein.
  • Ci-C x includes C1-C2, C1-C3 . . . Ci-C x .
  • Ci-C x refers to the number of carbon atoms that make up the moiety to which it designates (excluding optional substituents).
  • an “alkyl” group refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation.
  • the “alkyl” group may have 1 to 18, 1 to 12, 1 to 10, 1 to 8, or 1 to 6 carbon atoms (whenever it appears herein, a numerical range such as “1 to 6” refers to each integer in the given range; e.g. , “ 1 to 6 carbon atoms” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated).
  • the alkyl group of the compounds described herein may be designated as “Ci-Cealkyl” or similar designations.
  • “Ci-Cealkyl” indicates that there are one to six carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, iso-pentyl, neopentyl, and hexyl.
  • Alkyl groups can be substituted or unsubstituted.
  • an alkyl group can be a monoradical or a diradical (i.e., an alkylene group).
  • alkoxy refers to a “-O-alkyl” group, where alkyl is as defined herein.
  • alkenyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond.
  • an alkenyl groups may have 2 to 6 carbons.
  • Alkenyl groups can be substituted or unsubstituted. Depending on the structure, an alkenyl group can be a monoradical or a diradical (i.e., an alkenylene group).
  • alkynyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond.
  • alkynyl group include -CoCH, -CoCCH 3 , -CoCCH 2 CH 3 and -CoCCH 2 CH 2 CH 3 .
  • an alkynyl group can have 2 to 6 carbons.
  • Alkynyl groups can be substituted or unsubstituted.
  • an alkynyl group can be a monoradical or a diradical (i.e., an alkynylene group).
  • Amino refers to a -NH 2 group.
  • “Dialkylamino” refers to a -N(alkyl) 2 group, where alkyl is as defined herein.
  • aromatic refers to a planar ring having a delocalized p-electron system containing 4n+2 p electrons, where n is an integer. Aromatic rings can be formed from five, six, seven, eight, nine, or more than nine atoms. Aromatics can be optionally substituted.
  • aromatic includes both aryl groups (e.g., phenyl, naphthalenyl) and heteroaryl groups (e.g., pyridinyl, quinolinyl).
  • aryl refers to a monocyclic aromatic ring wherein each of the atoms forming the ring is a carbon atom (e.g., phenyl) or a polycyclic ring system (e.g., bicyclic or tricyclic) wherein 1) at least one ring is carbocyclic and aromatic, 2) a bond to the remainder of the compound is directly bonded to a carbocyclic aromatic ring of the aryl ring system, and 3) the carbocyclic aromatic ring of the aryl ring system of 2) is not directly bonded (e.g., fused) to a heteroaryl ring in the polycyclic ring system.
  • a carbon atom e.g., phenyl
  • a polycyclic ring system e.g., bicyclic or tricyclic
  • Aryl rings can be formed by five, six, seven, eight, nine, or more than nine carbon atoms.
  • Aryl groups can be optionally substituted.
  • Examples of aryl groups include, but are not limited to phenyl, and naphthalenyl.
  • an aryl group can be a monoradical or a diradical (i.e., an arylene group).
  • the aryl radical is a monocyclic, bicyclic, or tricyclic ring system.
  • an aryl is a monocyclic ring.
  • an aryl is a fused ring polycyclic system.
  • an aryl is a bridged ring polycyclic system.
  • the aryl is a “fused ring aryl” wherein the aryl ring is fused with a cycloalkyl or a heterocycloalkyl ring.
  • Carboxy refers to -CO2H.
  • carboxy moieties may be replaced with a “carboxylic acid bioisostere”, which refers to a functional group or moiety that exhibits similar physical and/or chemical properties as a carboxylic acid moiety.
  • a carboxylic acid bioisostere has similar biological properties to that of a carboxylic acid group.
  • a compound with a carboxylic acid moiety can have the carboxylic acid moiety exchanged with a carboxylic acid bioisostere and have similar physical and/or biological properties when compared to the carboxylic acid-containing compound.
  • a carboxylic acid bioisostere would ionize at physiological pH to roughly the same extent as a carboxylic acid group.
  • bioisosteres of a carboxylic acid include, but are not limited to, and the like.
  • cycloalkyl refers to a monocyclic carbocyclic saturated or partially unsaturated non-aromatic ring or a polycyclic carbocyclic (i.e., does not include heteroatom(s)) ring system (e.g., bicyclic or tricyclic) wherein 1) at least one ring is carbocyclic saturated or partially unsaturated and non-aromatic, 2) a bond to the remainder of the compound is directly bonded to a carbocyclic saturated or partially unsaturated non-aromatic ring of the ring system, and 3) the carbocyclic saturated or partially unsaturated non-aromatic ring of the ring system of 2) is not directly bonded (e.g., fused or spirocyclic) to a heterocycloalkyl ring in the polycyclic ring system.
  • heteroatom(s) ring system
  • Cycloalkyls may be saturated or partially unsaturated.
  • a cycloalkyl ring is a spirocyclic cycloalkyl ring.
  • a cycloalkyl is a monocyclic ring.
  • a cycloalkyl is a fused ring polycyclic system.
  • a cycloalkyl is a bridged ring polycyclic system.
  • a cycloalkyl is a spirocyclic polycyclic ring system.
  • cycloalkyl groups include groups having from 3 to 10 ring atoms.
  • a cycloalkyl group can be a monoradical or a diradical (i.e., a cycloalkylene group).
  • heteroaryl or, alternatively, “heteroaromatic” refers to an monocyclic aryl group that includes one or more ring heteroatoms selected from nitrogen, oxygen and sulfur; or a polycyclic ring system (e.g., bicyclic or tricyclic) wherein 1) at least one ring is aromatic and includes one or more heteroatoms selected from nitrogen, oxygen and sulfur and 2) a bond to the remainder of the compound is directly bonded to an aromatic ring including one or more heteroatoms selected from nitrogen, oxygen and sulfur or an aromatic ring directly bonded (e.g., fused) to an aromatic ring including one or more heteroatoms selected from nitrogen, oxygen and sulfur, of the aryl ring system.
  • the heteroaryl radical may be a monocyclic, bicyclic, or tricyclic ring system, wherein at least one of the rings in the ring system is fully unsaturated (i.e., aromatic) and includes a heteroatom.
  • a heteroaryl is a monocyclic ring.
  • a heteroaryl is a fused ring polycyclic system.
  • a heteroaryl is a bridged ring polycyclic system.
  • Y-containing “heteroaromatic” or “heteroaryl” moiety refers to an aromatic group in which at least one of the skeletal atoms of the ring is a nitrogen atom.
  • a heteroaryl group can be a monoradical or a diradical (i.e., a heteroarylene group).
  • a “heterocycloalkyl” group or “heteroalicyclic” group refers to a cycloalkyl group, wherein at least one skeletal ring atom of a saturated or partially unsaturated non-aromatic ring is a heteroatom selected from nitrogen, oxygen, phosphorus, and sulfur.
  • a heterocycloalkyl refers to a monocyclic saturated or partially unsaturated nonaromatic ring including one or more heteroatoms or a polycyclic ring system (e.g., bicyclic or tricyclic) wherein 1) at least one ring is saturated or partially unsaturated, non-aromatic, and includes one or more heteroatoms and 2) a bond to the remainder of the compound is directly bonded to a ring of the ring system that is a saturated or partially unsaturated and non-aromatic ring that includes one or more heteroatoms or a non-aromatic ring directly bonded (e.g., fused) to a saturated or partially unsaturated and non-aromatic ring that includes one or more heteroatoms of the ring system.
  • a polycyclic ring system e.g., bicyclic or tricyclic
  • Heterocycloalkyls may be saturated or partially unsaturated.
  • the term heterocycloalkyl also includes all ring forms of the carbohydrates, including but not limited to the monosaccharides, the disaccharides and the oligosaccharides.
  • a heterocycloalkyl ring is a spirocyclic heterocycloalkyl ring.
  • a heterocycloalkyl is a monocyclic ring.
  • a heterocycloalkyl is a fused ring polycyclic system.
  • a heterocycloalkyl is a bridged ring polycyclic system.
  • a heterocycloalkyl is a spirocyclic polycyclic ring system. Unless otherwise noted, heterocycloalkyls have from 2 to 13 carbons in the ring or ring system. 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).
  • a heterocycloalkyl group can be a monoradical or a diradical (i.e., a heterocycloalkylene group).
  • halo or, alternatively, “halogen” means fluoro, chloro, bromo and iodo.
  • haloalkyl refers to an alkyl group that is substituted with one or more halogens.
  • the halogens may the same or they may be different.
  • Non-limiting examples of haloalkyls include -CH 2 C1, -CF , -CHF 2 , - CH 2 CF 3 , -CF 2 CF 3 , and the like.
  • fluoroalkyl and “fluoroalkoxy” include alkyl and alkoxy groups, respectively, that are substituted with one or more fluorine atoms.
  • fluoroalkyls include -CF 3 , -CHF 2 , -CH 2 F, - CH 2 CF 3 , -CF 2 CF 3 , -CF 2 CF 2 CF 3 , -CF(CH 3 ) 3 , and the like.
  • Non-limiting examples of fluoroalkoxy groups include - OCF 3 , -OCHF 2 , -OCH 2 F, -OCH 2 CF 3 , -OCF 2 CF 3 , -OCF 2 CF 2 CF 3 , -OCF(CH 3 ) 2 , and the like.
  • heteroalky lene linker refers to a divalent alkyl radical where one or more skeletal chain atoms is selected from an atom other than carbon, e.g. , oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof.
  • the heteroatom(s) may be placed at any interior position of the heteroalkyl group.
  • the heteroatom(s) may be placed at one or both terminal positions of the heteroalkylene linker (i.e., position(s) directly bonded to portion(s) of the molecule other than the heteroalkylene linker).
  • Examples include, but are not limited to, -CH 2 -0-, -CH 2 -CH 2 -0-, -CH 2 -NH-, -CH 2 -CH 2 -NH-, -CH 2 -N(CH 3 )-, -CH 2 -CH 2 -N(CH 3 )-, -CH 2 -S-, -CH 2 - CH 2 -S-, -CH 2 -CH 2 -S(0)-, -CH 2 -CH 2 -S(0) 2 -, -CH 2 -S(0)-, -CH 2 -S(0)-, -CH 2 -S(0) 2 -, -CH 2 -CH 2 -CH 2 -S(0)-, -CH 2 -CH 2 -CH 2 -S(0)-, -CH 2 -CH 2 -CH 2 -S(0)-, -CH 2 -CH 2 -CH 2 -S(0)-, -CH 2 -CH 2 -CH 2 -S
  • Examples include, but are not limited to, -0-CH 2 -, -0-CH 2 -CH 2 -, -NH-CH 2 -, -NH-CH 2 - CH 2 -, -N(CH 3 )-CH 2 -, -N(CH 3 )-CH 2 -CH 2 -, -S-CH 2 -, -S-CH 2 -CH 2 -, -S(0)-CH 2 -CH 2 -, -S(0) 2 -CH 2 -CH 2 -, -S(0) 2 -CH 2 -, -S(0)-CH 2 -, -S(0) 2 -CH 2 -, -S(0)-CH 2 -CH 2 -, -S(0)-CH 2 -CH 2 -, -S(0)-CH 2 -CH 2 -CH 2 -, -S(0) 2 -CH 2 -CH 2 -, -S(0) 2 -CH 2 -CH 2 -, -S(0) 2 -
  • heteroatoms may be consecutive, such as, by way of example, -CH 2 -NH-0- and -0-Si(CH 3 ) 2 -.
  • examples include, but are not limited to, -P(0)(CH 3 )-CH 2 -, -P(0)(CH 3 )-CH 2 -CH 2 -, -P(0)(CH 3 )-CH 2 -CH 2 -,-CH 2 -P(0)(CH 3 )-, -CH 2 -CH 2 -P(0)(CH 3 )-, and -CH 2 -CH 2 -CH 2 -P(0)(CH 3 )-.
  • heteroatoms may be consecutive, such as, by way of example, -CH 2 -NH-0- and -0-Si(CH 3 ) 2 -.
  • A“heteroalkylene linker” may have from 2 to 4 main chain atoms unless specified otherwise.
  • heteroalkyl refers to an alkyl radical where one or more skeletal chain atoms is selected from an atom other than carbon, e.g. , oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof.
  • the heteroatom(s) may be placed at any interior position of the heteroalkyl group.
  • heteroalkyl may have from 1 to 6 carbon atoms.
  • bond refers to a chemical bond between two atoms, or two moieties when the atoms joined by the bond are considered to be part of larger substructure.
  • moiety refers to a specific segment or functional group of a molecule. Chemical moieties are often recognized chemical entities embedded in or appended to a molecule.
  • substituent “R” appearing by itself and without a number designation refers to a substituent selected from among from alkyl, haloalkyl, heteroalkyl, alkenyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon), and heterocycloalkyl.
  • “Pharmaceutically acceptable salt” includes both acid and base addition salts.
  • a pharmaceutically acceptable salt of any one of the compounds described herein is intended to encompass any and all pharmaceutically suitable salt forms.
  • Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.
  • “Pharmaceutically acceptable acid addition salt” refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like. Also included are salts that are formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and. aromatic sulfonic acids, etc.
  • acetic acid trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like.
  • Exemplary salts thus include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinate suberates, sebacates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, and the like.
  • Acid addition salts of basic compounds are, in some embodiments, prepared by contacting the free base forms with a sufficient amount of the desired acid to produce the salt according to methods and techniques with which a skilled artisan is familiar.
  • “Pharmaceutically acceptable base addition salt” refers to those salts that retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from addition of an inorganic base or an organic base to the free acid. Pharmaceutically acceptable base addition salts are, in some embodiments, formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like.
  • Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, Y, ⁇ -dibcnzylcthylcncdiaminc.
  • polypeptide refers to polymers of amino acids of any length.
  • the polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids.
  • the terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component.
  • amino acid refers to either natural and/or unnatural or synthetic amino acids, including glycine and both the D or L optical isomers, and amino acid analogs and peptidomimetics.
  • polynucleotide refers to a polymeric form of nucleotides of any length, either deoxy ribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three dimensional structure, and may perform any function, known or unknown.
  • polynucleotides coding or noncoding regions of a gene or gene fragment, loci (locus) defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, short interfering RNA (siRNA), short-hairpin RNA (shRNA), micro-RNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers.
  • loci locus defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, short interfering RNA (siRNA), short-hairpin RNA (shRNA), micro-RNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polyn
  • a polynucleotide may comprise one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs, such as peptide nucleic acid (PNA), Morpholino and locked nucleic acid (LNA), glycol nucleic acid (GNA), threose nucleic acid (TNA), 2’-fluoro, 2’-OMe, and phosphorothiolated DNA. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component or other conjugation target.
  • modified nucleotides such as methylated nucleotides and nucleotide analogs, such as peptide nucleic acid (PNA), Morpholino and locked nucleic acid (LNA), glycol nucle
  • expression refers to the process by which a polynucleotide is transcribed from a DNA template (such as into and mRNA or other RNA transcript) and/or the process by which a transcribed mRNA is subsequently translated into peptides, polypeptides, or proteins.
  • Transcripts and encoded polypeptides may be collectively referred to as “gene product.” If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.
  • the terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, murines, simians, humans, farm animals, sport animals, and pets. Tissues, cells, and their progeny of a biological entity obtained in vivo or cultured in vitro are also encompassed.
  • therapeutic agent refers to a molecule or compound that confers some beneficial effect upon administration to a subject.
  • the beneficial effect includes enablement of diagnostic determinations; amelioration of a disease, symptom, disorder, or pathological condition; reducing or preventing the onset of a disease, symptom, disorder or condition; and generally counteracting a disease, symptom, disorder or pathological condition.
  • treatment or “treating,” or “palliating” or “ameliorating” are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results including but not limited to a therapeutic benefit and/or a prophylactic benefit.
  • therapeutic benefit is meant any therapeutically relevant improvement in or effect on one or more diseases, conditions, or symptoms under treatment.
  • the compositions may be administered to a subject at risk of developing a particular disease, condition, or symptom, or to a subject reporting one or more of the physiological symptoms of a disease, even though the disease, condition, or symptom may not have yet been manifested.
  • prophylactic benefit includes reducing the incidence and/or worsening of one or more diseases, conditions, or symptoms under treatment (e.g. as between treated and untreated populations, or between treated and untreated states of a subject).
  • the term “effective amount” or “therapeutically effective amount” refers to the amount of an agent that is sufficient to effect beneficial or desired results.
  • the therapeutically effective amount may vary depending upon one or more of: the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the manner of administration and the like, which can readily be determined by one of ordinary skill in the art.
  • An effective amount of an active agent may be administered in a single dose or in multiple doses.
  • a component may be described herein as having at least an effective amount, or at least an amount effective, such as that associated with a particular goal or purpose, such as any described herein.
  • the term “effective amount” also applies to a dose that will provide an image for detection by an appropriate imaging method.
  • the specific dose may vary depending on one or more of: the particular agent chosen, the dosing regimen to be followed, whether it is administered in combination with other compounds, timing of administration, the tissue to be imaged, and the physical delivery system in which it is carried.
  • in vivo refers to an event that takes place in a subject’s body.
  • ex vivo refers to an event that first takes place outside of the subject’s body for a subsequent in vivo application into a subject’s body.
  • ex vivo preparation may involve preparation of cells outside of a subject’s body for the purpose of introduction of the prepared cells into the same or a different subject’s body.
  • in vitro refers to an event that takes place outside of a subject’s body.
  • an in vitro assay encompasses any assay ran outside of a subject’s body.
  • In vitro assays encompass cell-based assays in which cells alive or dead are employed.
  • In vitro assays also encompass a cell-free assay in which no intact cells are employed.
  • Ras refers to a protein in the Rat sarcoma (Ras) superfamily of small GTPases, such as in the Ras subfamily.
  • the Ras superfamily includes, but is not limited to, the Ras subfamily, Rho subfamily, Rab subfamily, Rap subfamily, Arf subfamily, Ran subfamily, Rheb subfamily, RGK subfamily, Rit subfamily, Miro subfamily, and Unclassified subfamily.
  • a Ras protein is selected from the group consisting of KRAS (also used interchangeably herein as K-Ras, K-ras, Kras), HRAS (or H-Ras), NRAS (or N-Ras), MRAS (or M-Ras), ERAS (or E-Ras), RRAS2 (or R-Ras2), RALA (or RalA), RALB (or RalB), RIT1, and any combination thereof, such as from KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof.
  • KRAS also used interchangeably herein as K-Ras, K-ras, Kras
  • HRAS or H-Ras
  • NRAS or N-Ras
  • MRAS or M-Ras
  • ERAS or E-Ras
  • RRAS2 or R-Ras2
  • RALA or RalA
  • RALB or RalB
  • a mutant Ras refers to a Ras protein with one or more amino acid mutations, such as with respect to a common reference sequence such as a wild-type (WT) sequence.
  • a mutant Ras is selected from a mutant KRAS, mutant HRAS, mutant NRAS, mutant MRAS, mutant ERAS, mutant RRAS2, mutant RALA, mutant RALB, mutant RIT1, and any combination thereof, such as from a mutant KRAS, mutant HRAS, mutant NRAS, mutant RALA, mutant RALB, and any combination thereof.
  • a mutation can be an introduced mutation, a naturally occurring mutation, or a non-naturally occurring mutation.
  • a mutation can be a substitution (e.g., a substituted amino acid), insertion (e.g., addition of one or more amino acids), or deletion (e.g., removal of one or more amino acids).
  • two or more mutations can be consecutive, non-consecutive, or a combination thereof.
  • a mutation can be present at any position of Ras.
  • a mutation can be present at position 12, 13, 62, 92, 95, or any combination thereof of Ras relative to SEQ ID No. 1 when optimally aligned.
  • a mutant Ras may comprise about or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or more than 50 mutations. In some embodiments, a mutant Ras may comprise up to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 mutations.
  • the mutant Ras is about or up to about 500, 400, 300, 250, 240, 233, 230, 220, 219, 210, 208, 206, 204, 200, 195, 190, 189, 188, 187, 186, 185, 180, 175, 174, 173, 172, 171, 170, 169, 168, 167, 166, 165, 160, 155, 150, 125, 100, 90, 80, 70, 60, 50, or fewer than 50 amino acids in length.
  • an amino acid of a mutation is a proteinogenic, natural, standard, non-standard, non- canonical, essential, non-essential, or non-natural amino acid.
  • an amino acid of a mutation has a positively charged side chain, a negatively charged side chain, a polar uncharged side chain, a non-polar side chain, a hydrophobic side chain, a hydrophilic side chain, an aliphatic side chain, an aromatic side chain, a cyclic side chain, an acyclic side chain, a basic side chain, or an acidic side chain.
  • a mutation comprises a reactive moiety.
  • a substituted amino acid comprises a reactive moiety.
  • a mutant Ras can be lurther modified, such as by conjugation with a detectable label.
  • a mutant Ras is a full-length or truncated polypeptide.
  • a mutant Ras can be a truncated polypeptide comprising residues 1-169 or residues 11-183 (e.g., residues 11-183 of a mutant RALA or mutant RALB).
  • [00144] indicates the location of attachment (e.g., location of a bond to another atom) of the depicted chemical formula or atom to a substituent, a further component of a molecule, or an atom.
  • a substituent e.g., location of a bond to another atom
  • a further component of a molecule e.g., a further component of a molecule
  • an atom e.g., a further component of a molecule, or an atom.
  • a selected residue in a protein corresponds to Cysl2 of a human Ras (e.g., human K-Ras) protein when the selected residue occupies the same essential spatial or other structural position as Cysl2 in the human Ras (e.g., human K-Ras) protein.
  • a selected protein is aligned for maximum homology with the human Ras (e.g., human K-Ras) protein
  • the position in the aligned selected protein aligning with Cysl2 is said to correspond to Cysl2.
  • a three dimensional structural alignment can also be used, e.g., where the structure of the selected protein is aligned for maximum correspondence with the human K-Ras protein and the overall structures compared.
  • an amino acid that occupies the same essential position as Cysl2 in the structural model is said to correspond to the Cysl2 residue.
  • a selected residue in a protein corresponds to Cysl3 of a human Ras (e.g., human K-Rasa) protein when the selected residue occupies the same essential spatial or other structural position as Cysl3 in a human Ras (e.g., human K-Ras) protein, similar to the example of Cysl2 above.
  • a human Ras e.g., human K-Rasa
  • a C3-iocycloalkyl is a 3 membered cycloalkyl. In embodiments, a C3-iocycloalkyl is a 4 membered cycloalkyl. In embodiments, a C3-iocycloalkyl is a 5 membered cycloalkyl. In embodiments, a C3- l ocycloalkyl is a 6 membered cycloalkyl. In embodiments, a C3-iocycloalkyl is a 7 membered cycloalkyl. In embodiments, a C3-iocycloalkyl is a 8 membered cycloalkyl.
  • a C3-iocycloalkyl is a 9 membered cycloalkyl. In embodiments, a C3-iocycloalkyl is a 10 membered cycloalkyl. In embodiments, a C3-iocycloalkyl is a 3-10 membered cycloalkyl. In embodiments, a C2-9heterocycloalkyl is a 3 membered heterocycloalkyl. In embodiments, a C2-9heterocycloalkyl is a 4 membered heterocycloalkyl. In embodiments, a C2-9heterocycloalkyl is a 5 membered heterocycloalkyl.
  • a C2-9heterocycloalkyl is a 6 membered heterocycloalkyl. In embodiments, a C2-9heterocycloalkyl is a 7 membered heterocycloalkyl. In embodiments, a C2-9heterocycloalkyl is a 8 membered heterocycloalkyl. In embodiments, a C2-9heterocycloalkyl is a 9 membered heterocycloalkyl. In embodiments, a C2-9heterocycloalkyl is a 10 membered heterocycloalkyl. In embodiments, a C2-9heterocycloalkyl is a ll membered heterocycloalkyl.
  • a C2-9heterocycloalkyl is a 12 membered heterocycloalkyl. In embodiments, a C2-9heterocycloalkyl is a 3-12 membered heterocycloalkyl. In embodiments, a C2- li heterocycloalkyl is a 3 membered heterocycloalkyl. In embodiments, a C2-iiheterocycloalkyl is a 4 membered heterocycloalkyl. In embodiments, a C2-iiheterocycloalkyl is a 5 membered heterocycloalkyl. In embodiments, a C2-iiheterocycloalkyl is a 6 membered heterocycloalkyl.
  • a C2-iiheterocycloalkyl is a 7 membered heterocycloalkyl. In embodiments, a C2-iiheterocycloalkyl is a 8 membered heterocycloalkyl. In embodiments, a C2-iiheterocycloalkyl is a 9 membered heterocycloalkyl. In embodiments, a C2-iiheterocycloalkyl is a 10 membered heterocycloalkyl. In embodiments, a C2-iiheterocycloalkyl is a 11 membered heterocycloalkyl. In embodiments, a C2-iiheterocycloalkyl is a 12 membered heterocycloalkyl.
  • a C2-iiheterocycloalkyl is a 3-12 membered heterocycloalkyl.
  • a Ci-nheterocycloalkyl is a 3 membered heterocycloalkyl.
  • a Ci-nheterocycloalkyl is a 4 membered heterocycloalkyl.
  • a Ci-nheterocycloalkyl is a 5 membered heterocycloalkyl.
  • a Ci-nheterocycloalkyl is a 6 membered heterocycloalkyl.
  • a Ci-nheterocycloalkyl is a 7 membered heterocycloalkyl.
  • a Ci-nheterocycloalkyl is a 8 membered heterocycloalkyl. In embodiments, a Ci-nheterocycloalkyl is a 9 membered heterocycloalkyl. In embodiments, a Ci-nheterocycloalkyl is a 10 membered heterocycloalkyl. In embodiments, a Ci-nheterocycloalkyl is a 11 membered heterocycloalkyl. In embodiments, a Ci-nheterocycloalkyl is a 12 membered heterocycloalkyl. In embodiments, a Ci-nheterocycloalkyl is a 3-12 membered heterocycloalkyl.
  • a C6-i2aryl is a 6 membered aryl. In embodiments, a C6-i2aryl is a 7 membered aryl. In embodiments, a C6-i2aryl is a 8 membered aryl. In embodiments, a C6-i2aryl is a 9 membered aryl. In embodiments, a C6-i2aryl is a 10 membered aryl. In embodiments, a C6-i2aryl is a 11 membered aryl. In embodiments, a C6-i2aryl is a 12 membered aryl.
  • a C6-i2aryl is a 6-12 membered aryl.
  • a Ci-nheteroaryl is a 5 membered heterocycloalkyl.
  • a Ci-nheteroaryl is a 6 membered heterocycloalkyl.
  • a Ci- nheteroaryl is a 7 membered heterocycloalkyl.
  • a Ci-nheteroaryl is a 8 membered heterocycloalkyl.
  • a Ci-nheteroaryl is a 9 membered heterocycloalkyl.
  • a Ci-nheteroaryl is a 10 membered heterocycloalkyl. In embodiments, a Ci-nheteroaryl is a 11 membered heterocycloalkyl. In embodiments, a Ci-nheteroaryl is a 12 membered heterocycloalkyl. In embodiments, a Ci-nheteroaryl is a 5-12 membered heterocycloalkyl. In embodiments, a C3-6cycloalkyl is a 3 membered cycloalkyl. In embodiments, a C3- 6 cycloalkyl is a 4 membered cycloalkyl.
  • a C3-6cycloalkyl is a 5 membered cycloalkyl. In embodiments, a C3-6cycloalkyl is a 6 membered cycloalkyl. In embodiments, a C 6 -ioaryl is a 6 membered aryl. In embodiments, a C 6 -ioaryl is a 7 membered aryl. In embodiments, a C 6 -ioaryl is a 8 membered aryl. In embodiments, a C 6 -ioaryl is a 9 membered aryl. In embodiments, a C 6 -ioaryl is a 10 membered aryl.
  • a Ci- gheteroaryl is a 5 membered heterocycloalkyl. In embodiments, a Ci-gheteroaryl is a 6 membered heterocycloalkyl. In embodiments, a Ci-gheteroaryl is a 7 membered heterocycloalkyl. In embodiments, a Ci-gheteroaryl is a 8 membered heterocycloalkyl. In embodiments, a Ci-gheteroaryl is a 9 membered heterocycloalkyl. In embodiments, a Ci-gheteroaryl is a 10 membered heterocycloalkyl.
  • a Ci-gheteroaryl is a 11 membered heterocycloalkyl.
  • a Cj-dictcroaryl is a 12 membered heterocycloalkyl.
  • a Ci- yhctcroan l is a 5-12 membered heterocycloalkyl.
  • W is C(O), S(O), or S(0) 2 ;
  • V is C(R 17 ) and J is C(R 16 ), or V is C(R 17 ) and J is N, or J is C(R 17 ) and V is C(R 16 ), or J is C(R 17 ) and V is N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • R 7 is a 3-12 membered nitrogen containing heterocycloalkyl or 5-12 membered nitrogen containing heteroaryl, wherein the 3-12 membered nitrogen containing heterocycloalkyl or 5-12 membered nitrogen containing heteroaryl are optionally substituted with one or more R 1 , one or more R 4 , or one or more R 6 ; wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i 2 cycloalkyl, Ci-nheterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl, wherein the C3-i 2 cycloalkyl, Ci-nheterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl are optionally substituted with one, two, or three R 20a ; each R 1 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, Ci-Cealkyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, - S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, - N(R 14 )C(0)0-, and -N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C 2 - dictcrocycloalkyl. C 6 -ioaryl, Ci-dictcroaiyl.
  • R 17 is -LkR 19 ;
  • L 1 is selected from a bond, Ci-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc ), and C(R
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), - C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , - S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )
  • R lc is selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, CV,- ioaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 201
  • R 19 is selected from a C3-i2cycloalkyl, C2-nheterocycloalkyl, C6-i2aryl, and C2-i2heteroaryl, wherein the C3- ncycloalkyl, C2-iiheterocycloalkyl, C6-i2aryl, and C2-i2heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3- 6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , - 0C(0)N(R 12 )(R
  • R 16 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C 2 - gheterocycloalkyl, C 6 -ioaryl, Ci- ⁇ ) hctcroan l.
  • R 12a is selected from Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, G- gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CEC-G-ioaryl, -CH2-Ci-9heteroaryl, and Ci- gheteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, G- gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CEC-G-ioaryl, -CH2-Ci-9heteroaryl, and Ci- gheteroary
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, G- gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CEh-Ci-gheteroaryl, and Ci- gheteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C 2 - gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CEh-Ci-ghe
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci ⁇ alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C 2 - gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S
  • Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 20f ; each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , and R 201 are each independently selected from halogen, -CN, Ci- 6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2- gheterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH2-Ci-9he
  • W is C(O), S(O), or S(0) 2 ;
  • V is C(R 17 ) and J is C(R 16 ), or V is C(R 17 ) and J is N, or J is C(R 17 ) and V is C(R 16 ), or J is C(R 17 ) and V is N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • R 7 is a 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, or 5-12 membered heteroaryl, wherein the 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, or 5-12 membered heteroaryl are optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i2cycloalkyl, Ci-nhetero
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, G-Galkyl, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, - S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, - N(R 14 )C(0)0-, and -N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0) 2 R
  • R 17 is -G-R 19 ;
  • L 1 is selected from a bond, G-Galkyl, C2-C6alkenyl, G-Galkynyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc ), and C(R l
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-dictcroarvl.
  • gheterocycloalkyl, C 6 -ioaryl, and Ci-dictcroarvl are optionally substituted with one, two, or three R 201 ; or R lf and R lg are joined to form a 4-7 membered heterocycloalkyl ring or a 4-7 membered cycloalkyl ring, wherein the 4-7 membered heterocycloalkyl ring or 4-7 membered cycloalkyl ring are optionally substituted with one, two, or three R 201 ;
  • R lc is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, CV,. ioaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 201
  • R 19 is selected from a C3-i 2 cycloalkyl, C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl, wherein the C3- i 2 cycloalkyl.
  • C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3- 6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , - 0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)
  • R 16 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0)
  • R 12a is selected from Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -C(R 12c ) 2 -C3-iocycloalkyl, C 2.
  • R 12b is selected from hydrogen, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocyeloalkyl, C 2 - gheterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocyeloalkyl, C6-ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci- 9 heteroaryl, and Ci-gheteroaryl, wherein Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocyeloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2
  • R 12c is independently selected from hydrogen and R 20k ;
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2 - gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 ,
  • each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -C 1 - gheteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -io
  • Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 20f ; each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 201 , and R 20k are each independently selected from halogen, oxo, - CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2 - gheterocycloalkyl, C 6 -ioaryl, -CH 2
  • X is C(R 3 ). In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, X is N.
  • V is C(R 16 ) and J is C(R 17 ). In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, V is N and J is C(R 17 ). In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, J is N and V is C(R 17 ). In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, J is C(R 16 ) and V is C(R 17 ). In further embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, W is C(O). In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, W is S(O). In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, W is S(0) 2 .
  • the compound has the structure: Formula (IA6), 12).
  • the compound has the structure: ), , 2).
  • L 7 is a bond. In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, L 7 is -NH-.
  • L 7 is a bond. In embodiments, L 7 is -0-. In embodiments, L 7 is -N(R 14 )-. In embodiments, L 7 is -C(O)-. In embodiments, L 7 is -N(R 14 )C(0)-. In embodiments, L 7 is -C(0)N(R 14 )-. In embodiments, L 7 is -S-. In embodiments, L 7 is -S(0) 2 -. In embodiments, L 7 is -S(O)-. In embodiments, L 7 is - S(0) 2 N(R 14 )-. In embodiments, L 7 is -S(0)N(R 14 )-.
  • L 7 is -N(R 14 )S(0)-. In embodiments, L 7 is - N(R 14 )S(0) 2 -. In embodiments, L 7 is Ci-Cealkyl. In embodiments, L 7 is C2-C6alkenyl. In embodiments, L 7 is C2- Cealkynyl. In embodiments, L 7 is 2 to 4 membered heteroalkylene linker. In embodiments, L 7 is Ci-Cealkyl optionally substituted with one, two, or three R 20a . In embodiments, L 7 is C2-C6alkenyl optionally substituted with one, two, or three R 20a .
  • L 7 is C2-Cealkynyl optionally substituted with one, two, or three R 20a . In embodiments, L 7 is 2 to 4 membered heteroalkylene linker optionally substituted with one, two, or three R 20a . In embodiments, L 7 is -N(H)-. In embodiments, L 7 is -N(H)C(0)-. In embodiments, L 7 is -C(0)N(H)-. In embodiments, L 7 is -S(0) 2 N(H)-. In embodiments, L 7 is -S(0)N(H)-. In embodiments, L 7 is -N(H)S(0)-. In embodiments, L 7 is -N(H)S(0) 2 -.
  • R 7 is a 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl, wherein the 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the a 4- 12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl are optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent
  • R 7 is a 3-12 membered nitrogen containing heterocycloalkyl, wherein the 3-12 membered nitrogen containing heterocycloalkyl is optionally substituted with one or more R 1 , one or more R 4 , or one or more R 6 ; and wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i2cycloalkyl, Ci-nheterocycloalkyl, C6-i2aryl, or Ci-nheteroaryl, wherein the C3-i2cycloalkyl, Ci- li heterocycloalkyl, C6-i2aryl, or Ci-nheteroaryl are optionally substituted with one, two, or three R 20a .
  • R 7 is a 3-12 membered nitrogen containing heterocycloalkyl, wherein the 3-12 membered nitrogen containing heterocycloalkyl is optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; and wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i2cycloalkyl, Ci-nheterocycloalkyl, G,.
  • naryl, or Ci-nheteroaryl wherein the C3-i2cycloalkyl, Ci-nheterocycloalkyl, C6-i2aryl, or G-iiheteroaryl are optionally substituted with one, two, or three R 20a .
  • R 7 is a 3-12 membered cycloalkyl. In embodiments, R 7 is a 5-12 membered cycloalkyl.
  • R 7 is 3-12 membered heterocycloalkyl. In embodiments, R 7 is 6-12 membered aryl. In embodiments, R 7 is 7-12 membered aryl. In embodiments, R 7 is 5-12 membered heteroaryl.
  • R 7 is a 3-12 membered cycloalkyl comprising one or more ring nitrogen atoms. In embodiments, R 7 is a 5-12 membered cycloalkyl comprising one or more ring nitrogen atoms. In embodiments, R 7 is 3-12 membered heterocycloalkyl comprising one or more ring nitrogen atoms. In embodiments, R 7 is 6-12 membered aryl comprising one or more ring nitrogen atoms. In embodiments, R 7 is 7-12 membered aryl comprising one or more ring nitrogen atoms. In embodiments, R 7 is 5-12 membered heteroaryl comprising one or more ring nitrogen atoms.
  • R 7 is a 3-12 membered cycloalkyl comprising one or more ring oxygen atoms. In embodiments, R 7 is a 5-12 membered cycloalkyl comprising one or more ring oxygen atoms. In embodiments, R 7 is 3-12 membered heterocycloalkyl comprising one or more ring oxygen atoms. In embodiments, R 7 is 6-12 membered aryl comprising one or more ring oxygen atoms. In embodiments, R 7 is 7-12 membered aryl comprising one or more ring oxygen atoms. In embodiments, R 7 is 5-12 membered heteroaryl comprising one or more ring oxygen atoms.
  • R 7 is a 3-12 membered cycloalkyl optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is a 5-12 membered cycloalkyl optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 3-12 membered heterocycloalkyl optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 6-12 membered aryl optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 7-12 membered aryl optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 5-12 membered heteroaryl optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is a 3-12 membered cycloalkyl comprising one or more ring nitrogen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is a 5-12 membered cycloalkyl comprising one or more ring nitrogen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 3-12 membered heterocycloalkyl comprising one or more ring nitrogen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 6-12 membered aryl comprising one or more ring nitrogen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 7-12 membered aryl comprising one or more ring nitrogen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 5-12 membered heteroaryl comprising one or more ring nitrogen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is a 3-12 membered cycloalkyl comprising one or more ring oxygen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is a 5-12 membered cycloalkyl comprising one or more ring oxygen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 3-12 membered heterocycloalkyl comprising one or more ring oxygen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 6-12 membered aryl comprising one or more ring oxygen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 7-12 membered aryl comprising one or more ring oxygen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is 5-12 membered heteroaryl comprising one or more ring oxygen atoms optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 .
  • R 7 is a C3cycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cicycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cecycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a C7cycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a Ciocycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a monocyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a monocyclic Cicycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cecycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic C7cycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Ciocycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cecycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C7cycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cecycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Ciocycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cecycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C7cycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Ciocycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cecycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic C7cycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Ciocycloalkyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cecycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a C7cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Ciocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cecycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C7cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Ciocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cecycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C7cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Ciocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cecycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic C7cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Ciocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cicycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cecycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a C7cycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a Ciocycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cicycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cecycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic C7cycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a monocyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a monocyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a monocyclic Ciocycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cecycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C7cycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Ciocycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cecycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C7cycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Ciocycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cecycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic C7cycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Ciocycloalkyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cecycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a C7cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Ciocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cecycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C7cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a fused bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a fused bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Ciocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cecycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C7cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Ciocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cecycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic C7cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Ciocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a C7cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a Ciocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a fused bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C7cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Ciocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C7cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Ciocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic C7cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Ciocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a C7cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Ciocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C7cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Ciocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C7cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Ciocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cecycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic C7cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cscycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Cycvcloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic Ciocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 12 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 5 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 5 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 5 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 9 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 10 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 11 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 12 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 5 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 5 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 5 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered cycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 12 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 5 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 5 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 5 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 9 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 10 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 11 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 12 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 5 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 5 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 5 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered cycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 3 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 4 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 12 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 3 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 4 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 3 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 4 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 11 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 12 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 3 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 4 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 5 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered heterocycloalkyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 3 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 4 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 12 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 3 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 4 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 3 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 4 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 12 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 3 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 4 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 5 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered heterocycloalkyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cearyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a C-aiyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cearyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cioaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cearyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic C-aiy 1 optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Csaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cearyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cioaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cearyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C-aiyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Co aryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cioaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cearyl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C-arvl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Coaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cioaryl optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a C-arvl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cioaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cearyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C-arvl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic arvl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cioaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cearyl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C-arvl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic arvl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cioaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cearyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a C-arvl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Co aryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cioaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cearyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic C-aiy 1 optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Csaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Gaiyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic Cioaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a fused bicyclic Csaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a fused bicyclic C-arv 1 optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a fused bicyclic Csaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Gaiyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cioaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cearyl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Caryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Caryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cioaryl optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Caryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cioaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cearyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Caryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Caryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cioaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cearyl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Caryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Caryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cioaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a C-arvl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cyarvl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a Cioaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Giaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C-arvl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Coaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cioaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cearyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C-arvl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cearyl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cioaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a C-arvl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Csaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a Cioaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cearyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic C-arvl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Csaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cearyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic Cioaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cearyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic C-aiyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Csaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cyaiyl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic Cioaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 12 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered aryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 12 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered aryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 12 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered aryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 10 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 11 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 12 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered aryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 5 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 11 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 12 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 11 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 12 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 11 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 12 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 5 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered heteroaryl including at least one nitrogen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 5 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 6 and optionally substituted with one or more R 4 .
  • R 7 is a 5 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . [00243] In embodiments, R 7 is a monocyclic 5 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 . In embodiments, R 7 is a monocyclic 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a monocyclic 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a fused bicyclic 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a bridged bicyclic 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 6 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 7 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 8 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 9 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 7 is a spirocyclic bicyclic 10 membered heteroaryl including at least one oxygen atom and optionally substituted with one R 1 and optionally substituted with one or more R 4 .
  • R 4 is independently halogen. In embodiments, R 4 is independently R 4 is independently oxo. In embodiments, R 4 is independently -CN. In embodiments, R 4 is independently Ci- 6 alkyl. In embodiments,
  • R 4 is independently C2-6alkenyl. In embodiments, R 4 is independently C2-6alkynyl. In embodiments, R 4 is independently Ci- 6 haloalkyl. In embodiments, R 4 is independently C3-i2cycloalkyl. In embodiments, R 4 is independently -CH2-C3-i2cycloalkyl. In embodiments, R 4 is independently Ci-nheterocycloalkyl. In embodiments, R 4 is independently -CtC-Ci-nheterocycloalkyl. In embodiments, R 4 is independently C6-i2aryl. In embodiments,
  • R 4 is independently -CH 2 -C6-i2aryl. In embodiments, R 4 is independently -CtC-Ci-nheteroaryl. In embodiments, R 4 is independently Ci-nheteroaryl. In embodiments, R 4 is independently -OR 12 . In embodiments, R 4 is independently -SR 12 . In embodiments, R 4 is independently -N(R 12 )(R 13 ). In embodiments, R 4 is independently -C(0)0R 12 . In embodiments, R 4 is independently -0C(0)N(R 12 )(R 13 ). In embodiments, R 4 is independently - N(R 14 )C(0)N(R 12 )(R 13 ).
  • R 4 is independently -N(R 14 )C(0)0R 15 . In embodiments, R 4 is independently -N(R 14 )S(0) 2 R 15 . In embodiments, R 4 is independently -C(0)R 15 . In embodiments, R 4 is independently -S(0)R 15 . In embodiments, R 4 is independently -0C(0)R 15 . In embodiments, R 4 is independently - C(0)N(R 12 )(R 13 ). In embodiments, R 4 is independently -C(0)C(0)N(R 12 )(R 13 ). In embodiments, R 4 is independently -N(R 14 )C(0)R 15 . In embodiments, R 4 is independently -S(0) 2 R 15 .
  • R 4 is independently C2-6alkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently C2-6alkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Ci- 6 haloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently C3-i2cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently -CH2-C3- ncycloalkyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently Ci- li heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently -CH2-C1- li heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently C6-i2aryl optionally substituted with one, two, or three R 20a .
  • R 4 is independently -CH 2 -C6-i2aryl optionally substituted with one, two, or three R 20a .
  • R 4 is independently -CtC-Ci-nheteroaryl optionally substituted with one, two, or three R 20a .
  • R 4 is independently Ci-nheteroaryl optionally substituted with one, two, or three R 20a .
  • L 2 is a bond. In embodiments, L 2 is Ci-Cealkyl. In embodiments, L 2 is -0-. In embodiments, L 2 is -N(R 14 )-. In embodiments, L 2 is -C(O)-. In embodiments, L 2 is -N(R 14 )C(0)-. In embodiments, L 2 is -C(0)N(R 14 )-. In embodiments, L 2 is -S-. In embodiments, L 2 is -S(0) 2 -. In embodiments, L 2 is -S(O)-. In embodiments, L 2 is -S(0) 2 N(R 14 )-.
  • L 2 is -S(0)N(R 14 )-. In embodiments, L 2 is -N(R 14 )S(0)-. In embodiments, L 2 is -N(R 14 )S(0) 2 -. In embodiments, L 2 is -OCON(R 14 )-. In embodiments, L 2 is -N(R 14 )C(0)0-. In embodiments, L 2 is -N(R 14 )C(0)N(R 14 )-. In embodiments, L 2 is -N(H)-. In embodiments, L 2 is -N(H)C(0)-. In embodiments, L 2 is -C(0)N(H)-. In embodiments, L 2 is -S(0) 2 N(H)-.
  • L 2 is -S(0)N(H)-. In embodiments, L 2 is -N(H)S(0)-. In embodiments, L 2 is -N(H)S(0) 2 -. In embodiments, L 2 is -OCON(H)-. In embodiments, L 2 is -N(H)C(0)0-. In embodiments, L 2 is -N(H)C(0)N(R 14 )-.
  • R 4 is independently Cialkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently C2alkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cialkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cialkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cialkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cealkyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently C2alkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cialkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cialkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Csalkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cealkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently C2alkynyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently Cialkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cialkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Csalkynvi optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cealkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihaloalkyl. In embodiments, R 4 is independently Cihaloalkyl. In embodiments, R 4 is independently Cihaloalkyl. In embodiments, R 4 is independently Cihaloalkyl. In embodiments, R 4 is independently Cihaloalkyl. In embodiments, R 4 is independently Cihaloalkyl. In embodiments, R 4 is independently Cehaloalkyl. In embodiments, R 4 is independently Cehaloalkyl.
  • R 4 is independently Ci cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cicycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cecycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently C7cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Ciocyclo
  • R 4 is independently Cihetcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihetcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihetcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihetcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Ceheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently Ciheterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Gsaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently C-arvl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Csaryl optionally substituted with one, two, or three R 20a .
  • R 4 is independently Csaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cioaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cnaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cnaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a .
  • R 4 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Ceheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Csheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cioheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently Cioheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is
  • R 4 is independently 3 membered cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 4 membered cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 5 membered cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 6 membered cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 7 membered cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently 8 membered cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 9 membered cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 10 membered cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently 3 membered heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 4 membered heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 5 membered heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 6 membered heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 7 membered heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 4 is independently 8 membered heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 9 membered heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 10 membered heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 6 membered aryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 7 membered aryl optionally substituted with one, two, or three R 20a .
  • R 4 is independently 8 membered aryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 9 membered aryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 10 membered aryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 11 membered aryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 12 membered aryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 5 membered heteroaryl optionally substituted with one, two, or three R 20a .
  • R 4 is independently 6 membered heteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 7 membered heteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 8 membered heteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 9 membered heteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 10 membered heteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 11 membered heteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 4 is independently 12 membered heteroaryl optionally substituted with one, two, or three R 20a .
  • R 4 is independently -OH. In embodiments, R 4 is independently -SH. In embodiments, R 4 is independently -NH 2 . In embodiments, R 4 is independently -C(0)OH. In embodiments, R 4 is independently - OC(0)NH 2 . In embodiments, R 4 is independently -N(H)C(0)NH 2 . In embodiments, R 4 is independently - N(H)C(0)OH. In embodiments, R 4 is independently -N(H)S(0) 2 CH 3 . In embodiments, R 4 is independently - C(0)H. In embodiments, R 4 is independently -S(0)CH 3 . In embodiments, R 4 is independently -0C(0)CH 3 .
  • R 4 is independently -OCH 3 . In embodiments, R 4 is independently -SCH 3 . In embodiments, R 4 is independently - N(CH 3 )(H). In embodiments, R 4 is independently -C(0)0CH 3 . In embodiments, R 4 is independently - 0C(0)N(CH 3 )(H). In embodiments, R 4 is independently -N(H)C(0)N(CH 3 )(H). In embodiments, R 4 is independently -N(H)C(0)0CH 3 . In embodiments, R 4 is independently -N(H)S(0) 2 CH 3 . In embodiments, R 4 is independently -C(0)CH 3 . In embodiments, R 4 is independently -S(0)CH 3 .
  • R 4 is independently -CH 2 N(H)C(0)CH 3 . In embodiments, R 4 is independently -CH 2 S(0) 2 CH 3 . In embodiments, R 4 is independently and -CH 2 S(0) 2 N(CH 3 )(H). In embodiments, R 4 is independently -0C(0)N(CH 3 ) 2 . In embodiments, R 4 is independently -N(H)C(0)N(CH 3 ) 2 . In embodiments, R 4 is independently -C(0)(CH 3 ). In embodiments, R 4 is independently -C(0)N(CH 3 ) 2 . In embodiments, R 4 is independently -C(0)C(0)N(CH 3 ) 2 . In embodiments, R 4 is independently -C(0)C(0)N(CH 3 ) 2 .
  • R 4 is capable of forming a covalent bond with the 12 th amino acid of a G12D KRas mutant. In embodiments, R 4 is capable of forming a covalent bond with the 12 th amino acid of a G12C KRas mutant. In embodiments, R 4 is capable of forming a covalent bond with the 12 th amino acid of a G12S KRas mutant. In embodiments, R 4 is capable of forming a covalent bond with the 13 th amino acid of a G13D KRas mutant. In embodiments, R 4 is capable of forming a covalent bond with the 13 th amino acid of a G13C KRas mutant. In embodiments, R 4 is capable of forming a covalent bond with the 13 th amino acid of a G13S KRas mutant.
  • R 4 is selected from the group consisting of
  • each R b is independently hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3- 6cycloalkyl, C2-7carboalkyl, C2-7carboxyalkyl, phenyl, or phenyl optionally substituted with one or more halogen, Ci- 6alkoxy, trifluoromethyl, amino, Ci-3alkylamino, C2-6dialkylamino, nitro
  • R 4 is independently selected from the group consisting of hydrogen, hydroxyl, C1-C6 alkoxy, and C1-C6 alkyl, or two R b are optionally join to form heterocycle having 3-12 ring atoms or C3-C6 cycloalkyl. In embodiments, R 4 is independently selected from the group consisting of
  • R 4 is independently -C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , or -C(0)R 15 . In embodiments, R 4 is independently -C(0)N(R 12 )(R 13 ). In embodiments, R 4 is independently -N(R 14 )C(0)R 15 . In embodiments, R 4 is independently -C(0)R 15 .
  • R 15 is C2-6alkenyl optionally substituted with one, two, or three R 20f , - C(0)R 15 wherein R 15 is C2-6alkynyl optionally substituted with one, two, or three R 20f , -C(0)R 15 wherein R 15 is C3- 6cycloalkyl optionally substituted with one, two, or three R 20f , -C(0)R 15 wherein R 15 is C2-9heterocycloalkyl optionally substituted with one, two, or three R 20f , -C(0)R 15 wherein R 15 is C 6 -ioaryl optionally substituted with one, two, or three R 20f , and -C(0)R 15 wherein R 15 is Ci-dictcroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)NH(R 12 ) and R 12 is independently Ci-dictcroaryl. wherein Ci- ihctcroaiyl is optionally substituted with one, two, or three R 20d .
  • R 4 is independently - C(0)NH(R 12 ) and R 12 is independently Ci-shctcroan l. wherein Ci-shctcroaiy l is optionally substituted with one, two, or three R 20d .
  • R 4 is independently -C(0)NH(R 12 ) and R 12 is independently Ci-ihctcroaryl.
  • R 12 is independently Cialkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently C2alkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently C2alkenyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkcnyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkcnyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkcnyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cealkenyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently C2alkynyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cialkynyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cialkynyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Csalkynyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cealkynyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cihaloalkyl. In embodiments, R 12 is independently Cihaloalkyl.
  • R 12 is independently Cihaloalkyl. In embodiments, R 12 is independently Cihaloalkyl. In embodiments, R 12 is independently Cshaloalkyl. In embodiments, R 12 is independently Cehaloalkyl.
  • R 12 is independently Cscycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cicycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cscycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cecycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently C7cycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cscycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cscycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Ciocycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cdictcrocycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cdictcrocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Ceheterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently C-hetcrocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cearyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently C-aryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Csaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Csaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cioaryl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Cnaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cnaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cihctcroaiyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cihctcroaiyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cihctcroaiy l optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently C die tcro aryl optionally substituted with one, two, or three R 20d .
  • R 12 is independently Ceheteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently C 7 he tcro aryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Csheteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cihctcroaiy l optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cioheteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently Cnheteroaryl optionally substituted with one, two, or three R 20d .
  • R 12 is independently 3 membered cycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 4 membered cycloalkyl optionally substituted with one, two, or three
  • R 20d is independently 5 membered cycloalkyl optionally substituted with one, two, or three
  • R 12 is independently 6 membered cycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 7 membered cycloalkyl optionally substituted with one, two, or three
  • R 20d is independently 8 membered cycloalkyl optionally substituted with one, two, or three
  • R 20d is independently 9 membered cycloalkyl optionally substituted with one, two, or three
  • R 20d is independently 10 membered cycloalkyl optionally substituted with one, two, or three
  • R 12 is independently 3 membered heterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 4 membered heterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 5 membered heterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 6 membered heterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 7 membered heterocycloalkyl optionally substituted with one, two, or three R 20d .
  • R 12 is independently 8 membered heterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 9 membered heterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 10 membered heterocycloalkyl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 6 membered aryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 7 membered aryl optionally substituted with one, two, or three R 20d .
  • R 12 is independently 8 membered aryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 9 membered aryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 10 membered aryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 11 membered aryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 12 membered aryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 5 membered heteroaryl optionally substituted with one, two, or three R 20d .
  • R 12 is independently 6 membered heteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 7 membered heteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 8 membered heteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 9 membered heteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 10 membered heteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 11 membered heteroaryl optionally substituted with one, two, or three R 20d . In embodiments, R 12 is independently 12 membered heteroaryl optionally substituted with one, two, or three R 20d .
  • R 15 is independently Cialkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C2alkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cialkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cialkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Csalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cealkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently C2alkenyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Ci alkenyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C4alkenyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Csalkcnyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cealkenyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C2alkynyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cialkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C4alkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Csalkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cealkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cihaloalkyl. In embodiments, R 15 is independently Cihaloalkyl.
  • R 15 is independently Cihaloalkyl. In embodiments, R 15 is independently Cihaloalkyl. In embodiments, R 15 is independently Cshaloalkyl. In embodiments, R 15 is independently Cehaloalkyl.
  • R 15 is independently Cscycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cicycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cscycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cecycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently C7cycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cscycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cscycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Ciocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cdictcrocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Ceheterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C-hetcrocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cearyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C-aiyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Csaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Csaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cioaryl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Cnaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cearyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cihctcroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cihctcroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cihctcroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cshctcroarvl optionally substituted with one, two, or three R 20f .
  • R 15 is independently Ceheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C-hetcroarvl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Csheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cdictcroarvl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cioheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Cnheteroaryl optionally substituted with one, two, or three R 20f .
  • R 15 is independently 3 membered cycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 4 membered cycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 5 membered cycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 6 membered cycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 7 membered cycloalkyl optionally substituted with one, two, or three R 20f .
  • R 20f is independently 8 membered cycloalkyl optionally substituted with one, two, or three
  • R 20f is independently 9 membered cycloalkyl optionally substituted with one, two, or three
  • R 20f is independently 10 membered cycloalkyl optionally substituted with one, two, or three
  • R 15 is independently 3 membered heterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 4 membered heterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 5 membered heterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 6 membered heterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 7 membered heterocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 15 is independently 8 membered heterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 9 membered heterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 10 membered heterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 6 membered aryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 7 membered aryl optionally substituted with one, two, or three R 20f .
  • R 15 is independently 8 membered aryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 9 membered aryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 10 membered aryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 11 membered aryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 12 membered aryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 5 membered heteroaryl optionally substituted with one, two, or three R 20f .
  • R 15 is independently 6 membered heteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 7 membered heteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 8 membered heteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 9 membered heteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 10 membered heteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 11 membered heteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently 12 membered heteroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and R 15 is independently selected from C2-6alkenyl, C2- 6 alkynyl, C2-s>heterocycloalkyl, and C’ l -yhctcroarvl. wherein C2-6alkenyl, C2-6alkynyl, C2-s>heterocycloalkyl, and Ci- yhctcroarvl are optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently C2alkenyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and R 15 is independently Cialkcnyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Cialkcnyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Csalkcnyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Cealkenyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and R 15 is independently C2alkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Cialkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Cialkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently - C(0)R 15 and R 15 is independently Csalkynyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and R 15 is independently Cealkynyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and R 15 is independently Cohctcrocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and R 15 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently - C(0)R 15 and R 15 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and R 15 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Ceheterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently C-hctcrocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Csheterocycloalkyl optionally substituted
  • R 4 is independently -C(0)R 15 and R 15 is independently Ciheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Ciheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Ciheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Ciheteroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -C(0)R 15 and R 15 is independently Cshctcroarvl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Ceheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Ciheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Csheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -C(0)R 15 and R 15 is independently Ceheteroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently selected from C2-6alkenyl, C2- 6 alkynyl, C2-9heterocycloalkyl, and C’ l -dictcroarvl. wherein C2-6alkenyl, C2-6alkynyl, C2-9heterocycloalkyl, and Ci- eheteroaryl are optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently C2alkenyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Cialkcnyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Cialkcnyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Csalkcnyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Cealkenyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently C2alkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Csalkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Cialkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Csalkynyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Cealkynyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently C 2 heterocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently C3heterocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently - NHC(0)R 15 and R 15 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Cshctcrocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Ceheterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently - NHC(0)R 15 and R 15 is independently C7heterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Cdictcrocycloalkyl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Ciheteroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently C 2 heteroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Cihctcroarvl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Ciheteroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Cshctcroarvl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Ceheteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently C7heteroaryl optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -NHC(0)R 15 and R 15 is independently Csheteroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is independently -NHC(0)R 15 and R 15 is independently Csheteroaryl optionally substituted with one, two, or three R 20f .
  • R 4 is capable of forming a covalent bond with a Ras amino acid sidechain. In embodiments, R 4 is capable of forming a covalent bond with a KRas amino acid. In embodiments, R 4 is capable of forming a covalent bond with the 12 th amino acid of a human KRas protein. In embodiments, R 4 is capable of forming a covalent bond with the 12 th amino acid of a mutant KRas protein selected from KRas G12D, KRas G12C, and KRas G12S. In embodiments, R 4 is capable of forming a covalent bond with the 13 th amino acid of a human KRas protein. In embodiments, R 4 is capable of forming a covalent bond with the 13 th amino acid of a mutant KRas protein selected from KRas G13D, KRas G13C, and KRas G13S.
  • R 4 is selected from
  • R 4 is selected from
  • R 15 is independently C 2-6 alkenyl optionally substituted with one, two, or three
  • R 15 is independently C 2-6 alkenyl optionally substituted with one, two, or three halogen. In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with one, two, or three F. In embodiments,
  • R 15 is independently C 2-6 alkenyl optionally substituted with -OR 21 . In embodiments, R 15 is independently C 2 - 6alkenyl optionally substituted with -N(R 22 )(R 23 ). In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with C 2-9 heterocycloalkyl. In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with Ci- 5 heteroaryl optionally substituted with one, two, or three Ci-6alkyl. In embodiments, R 15 is independently C 2 - 6alkenyl optionally substituted with Ci-shctcroarvl optionally substituted with methyl.
  • R 15 is independently C 2-6 alkenyl optionally substituted with -CN. In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with Ci-shctcroarvl optionally substituted with -N(R 24 )C(0)R 25 . In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with Ci- hctcroarvl and/or CN. In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with one, two, or three halogen.
  • R 15 is independently C 2-6 alkenyl optionally substituted with one, two, or three F. In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with -OR 21 . In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with -N(R 22 )(R 23 ). In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with C 2-9 heterocycloalkyl. In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with Ci-shctcroarvl optionally substituted with one, two, or three Ci-6alkyl.
  • R 15 is independently C 2-6 alkenyl optionally substituted with Ci-shctcroarvl optionally substituted with methyl. In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with - CN. In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with Ci-shctcroarvl optionally substituted with -N(R 24 )C(0)R 25 . In embodiments, R 15 is independently C 2-6 alkenyl optionally substituted with - C(0)N(R 22 )(R 23 ). In embodiments, R 15 is independently C 2-6 alkenyl substituted with Cl and optionally substituted with one or two R 20f .
  • R 15 is independently C 2-6 alkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with one, two, or three halogen. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with one, two, or three F. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with -OR 21 . In embodiments, R 15 is independently C 2 - 6alkynyl optionally substituted with -N(R 22 )(R 23 ). In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with C 2-9 heterocycloalkyl.
  • R 15 is independently C 2-6 alkynyl optionally substituted with Ci-sheteroaryl optionally substituted with one, two, or three Ci-6alkyl. In embodiments, R 15 is independently C 2 - 6alkynyl optionally substituted with Ci-shctcroarvl optionally substituted with methyl. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with -CN. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with Ci-sheteroaryl optionally substituted with -N(R 24 )C(0)R 25 .
  • R 15 is independently C 2-6 alkynyl optionally substituted with Ci-sheteroaryl and/or CN. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with one, two, or three halogen. In embodiments, R 15 is independently C 2 - 6 alkynyl optionally substituted with one, two, or three F. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with -OR 21 . In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with - N(R 22 )(R 23 ).
  • R 15 is independently C 2-6 alkynyl optionally substituted with C 2 -s > heterocycloalkyl. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with C’ l -shctcroarvl optionally substituted with one, two, or three Ci- 6 alkyl. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with Ci- sheteroaryl optionally substituted with methyl. In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with -CN.
  • R 15 is independently C 2-6 alkynyl optionally substituted with C’ l -shctcroarvl optionally substituted with -N(R 24 )C(0)R 25 . In embodiments, R 15 is independently C 2-6 alkynyl optionally substituted with -C(0)N(R 22 )(R 23 ). In embodiments, R 15 is independently C 2-6 alkynyl substituted with Cl and optionally substituted with one or two R 20f . In embodiments, R 15 is independently C 3 -scycloalkyl, optionally substituted with one, two, or three R 20f .
  • R 15 is independently C 3 -scycloalkyl, optionally substituted with Ci- 6 alkyl optionally substituted with one, two, or three halogen. In embodiments, R 15 is independently C 3 - scycloalkyl, optionally substituted with Ci- 6 alkyl optionally substituted with one, two, or three F. In embodiments, R 15 is independently Ci-shctcrocycloalkyl. optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Ci-shctcrocycloalkyl. optionally substituted with Ci- 6 alkyl optionally substituted with one, two, or three halogen.
  • R 15 is independently Ci-shctcrocycloalkyl. optionally substituted with Ci- 6 alkyl optionally substituted with one, two, or three F. In embodiments, R 15 is independently Ci- 6 alkyl, optionally substituted with one, two, or three R 20f . In embodiments, R 15 is independently Ci- 6 alkyl, substituted with Cl and optionally substituted with one, two, or three R 20f . In embodiments, R 4 is independently -CN.
  • L 2 is independently a bond, -C(0)NH-, -NHC(O)-, or -C(O)-; and R 5 is independently selected from halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -i 2 cycloalkyl, -CFF-Cs-ncycloalkyl, Ci- li heterocycloalkyl, -CFF-Ci-nheterocycloalkyl, Gs-naryl, -CH 2 -C 6 -i 2 aryl, -CFF-Ci-nheteroaryl, Ci-nheteroaryl, - OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ;
  • L 2 is independently -C(O)-; and R 5 is independently a Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -i 2 cycloalkyl, -CH 2 -C 3 -i 2 cycloalkyl, Ci-nheterocycloalkyl, -CFF-Ci-nheterocycloalkyl, C 6 -i 2 aryl, -CH 2 -C 6 -i 2 aryl, - CH 2 -Ci-nheteroaryl, or Ci-nheteroaryl, wherein the Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -i 2 cycloalkyl, -CH 2 -C 3 - ncycloalkyl, Ci-nheterocycloalkyl, -CFF-Ci-nheterocycloalkyl, C 6 -
  • L 2 is independently -C(O)-; and R 5 is independently a C 3 -i 2 cycloalkyl, Ci- li heterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl, wherein the C 3 -i 2 cycloalkyl, Ci-nheterocycloalkyl, C 6 -i 2 aryl, and Ci- nheteroaryl are optionally substituted with one, two, or three R 20a .
  • L 2 is independently a bond, -C(0)NH-, -NHC(O)-, or -C(O)-; L 2 is independently bonded to a carbon atom of R 5 ; and R 5 is independently selected from -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3- ncycloalkyl, C6-i2aryl, and Ci-nheteroaryl, wherein C h alky 1, C2-6alkenyl, C2-6alkynyl, C3-i2cycloalkyl, Gs-naryl, and Ci-iiheteroaryl, are optionally substituted with one, two, or three R 20a .
  • L 2 is independently -C(O)-; L 2 is independently bonded to a carbon atom of R 5 ; and R 5 is independently selected from Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-i2cycloalkyl, C6-i2aryl, and Ci-nheteroaryl, wherein the C h alky 1, C2-6alkenyl, C2-6alkynyl, C3-i2cycloalkyl, Gs-naryl, and Ci-nheteroaryl, are optionally substituted with one, two, or three R 20a .
  • L 2 is independently -C(O)-; L 2 is independently bonded to a carbon atom of R 5 ; and R 5 is independently selected from Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, and 5-6 membered heteroaryl, wherein the Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with one, two, or three R 20a .
  • L 2 is independently -C(O)-;
  • R 5 is independently ;
  • R 5a is independently CH, C(R 20a ), CH(R 20a ), QH, C(R 20a )2, N, NH, or N(R 20a );
  • R 5 comprises 0-3 independent R 20a ; and
  • 0-4 R 5a are independently N, NH, or N(R 20a ).
  • L 2 is independently -C(O)-; and R 5 is independently C3-iocycloalkyl, wherein C3- l ocycloalkyl is independently optionally substituted with one, two, or three R 20a .
  • L 2 is independently -C(O)-; and R 5 is independently cyclopropyl, wherein cyclopropyl is independently optionally substituted with one, two, or three F.
  • L 2 is independently -C(O)-; and R 5 is independently cyclopropyl, wherein cyclopropyl is independently optionally substituted with one, two, or three CN.
  • L 2 is independently -C(O)-; and R 5 is independently cyclopropyl, wherein cyclopropyl is independently optionally substituted with one, two, or three halogen.
  • R 5 is independently hydrogen. In embodiments, R 5 is independently halogen. In embodiments, R 5 is independently R 5 is independently oxo. In embodiments, R 5 is independently -CN. In embodiments, R 5 is independently Ci- 6 alkyl. In embodiments, R 5 is independently C2-6alkenyl. In embodiments, R 5 is independently C2-6alkynyl. In embodiments, R 5 is independently Ci- 6 haloalkyl. In embodiments, R 5 is independently C3-i2cycloalkyl. In embodiments, R 5 is independently -CH 2 -C3-i2cycloalkyl. In embodiments, R 5 is independently Ci-nheterocycloalkyl.
  • R 5 is independently -QH-Ci-nheterocycloalkyl. In embodiments, R 5 is independently C6-i2aryl. In embodiments, R 5 is independently -CH 2 -C6-i2aryl. In embodiments, R 5 is independently -Cfh-Ci-nheteroaryl. In embodiments, R 5 is independently Ci-nheteroaryl. In embodiments,
  • R 5 is independently -OR 12 . In embodiments, R 5 is independently -SR 12 . In embodiments, R 5 is independently - N(R 12 )(R 13 ). In embodiments, R 5 is independently -C(0)0R 12 . In embodiments, R 5 is independently - 0C(0)N(R 12 )(R 13 ). In embodiments, R 5 is independently -N(R 15 )C(0)N(R 12 )(R 13 ). In embodiments, R 5 is independently -N(R 15 )C(0)0R 15 . In embodiments, R 5 is independently -N(R 15 )S(0) 2 R 15 . In embodiments, R 5 is independently -C(0)R 15 .
  • R 5 is independently -CH 2 C(0)N(R 12 )(R 13 ). In embodiments, R 5 is independently -CH 2 N(R 15 )C(0)R 15 . In embodiments, R 5 is independently -CH 2 S(0) 2 R 15 . In embodiments, R 5 is independently and -CH 2 S(0) 2 N(R 12 )(R 13 ). In embodiments, R 5 is independently Ci- 6 alkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently C2-6alkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently C2-6alkynyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently Ci- 6 haloalkyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently C3-i2cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently -CH 2 -C3-i2cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently Ci-nheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently -Cfh-Ci-nheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently C6-i2aryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently -CH 2 -C6-i2aryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently -Cfh-Ci-nheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cmheteroaryl optionally substituted with one, two, or three R 20a .
  • R 5 is independently selected from hydrogen, halogen, oxo, -CN, Ci-ealkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), and -C(0)R 12 , wherein Ci- 6 alkyl, C2-6alkenyl, and C2-6alkynyl, are optionally substituted with one, two, or three R 20a .
  • R 5 is independently hydrogen.
  • R 5 is independently halogen.
  • R 5 is independently oxo. In some embodiments of the subject compound, R 5 is independently -CN. In additional embodiments of the subject compound, R 5 is independently Ci- 6 alkyl. In embodiments of the subject compound, R 5 is independently C 2 - 6 alkenyl. In some embodiments of the subject compound, R 5 is independently C2-6alkynyl. In further embodiments of the subject compound, R 5 is independently -OR 12 . In select embodiments of the subject compound, R 5 is independently -N(R 12 )(R 13 ). In additional embodiments of the subject compound, R 5 is independently -C(0)0R 12 .
  • R 5 is independently -0C(0)N(R 12 )(R 13 ). In some embodiments of the subject compound, R 5 is independently -C(0)R 12 . In select embodiments of the subject compound, R 5 is independently -NH 2 . In further embodiments of the subject compound, R 5 is independently -C(0)0H. In additional embodiments of the subject compound, R 5 is independently -0C(0)NH 2 . In embodiments of the subject compound, R 5 is independently -C(0)CH 3 .
  • R 5 is independently Cialkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently C2alkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cialkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cialkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Csalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cealkyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently C2alkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cialkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cialkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Csalkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cealkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently C2alkynyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently Cialkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cialkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Chalky m l optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cealkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cihaloalkyl. In embodiments, R 5 is independently C2haloalkyl. In embodiments, R 5 is independently Cihaloalkyl. In embodiments, R 5 is independently Cihaloalkyl. In embodiments, R 5 is independently Cshaloalkyl. In embodiments, R 5 is independently Cehaloalkyl. In embodiments, R 5 is independently Cehaloalkyl.
  • R 5 is independently Cicycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cicycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cecycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently C7cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Ciocycloal
  • R 5 is independently C2heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cshetcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Ceheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently C-hetcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 5 is independently Cearyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently C-arvl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Csaryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Csaryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cioaryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cnaryl optionally substituted with one, two, or three R 20a .
  • R 5 is independently Cearyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently C2heteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cshctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Ceheteroaryl optionally substituted with one, two, or three R 20a .
  • R 5 is independently C-hctcroaiy l optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Csheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cdictcroaiyl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cioheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently Cnheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 5 is independently -OH. In embodiments, R 5 is independently -SH.
  • R 5 is independently -NH 2 . In embodiments, R 5 is independently -C(0)0H. In embodiments, R 5 is independently - 0C(0)NH 2 . In embodiments, R 5 is independently -N(H)C(0)NH 2 . In embodiments, R 5 is independently - N(H)C(0)0H. In embodiments, R 5 is independently -N(H)S(0) 2 CH . In embodiments, R 5 is independently - C(0)H. In embodiments, R 5 is independently -S(0)CH . In embodiments, R 5 is independently -0C(0)CH 3 . In embodiments, R 5 is independently -C(0)NH 2 . In embodiments, R 5 is independently -C(0)C(0)NH 2 .
  • R 5 is independently -OCH 3 . In embodiments, R 5 is independently -SCH 3 . In embodiments, R 5 is independently -N(CH 3 )(H). In embodiments, R 5 is independently -C(0)0CH 3 . In embodiments, R 5 is independently -0C(0)N(CH 3 )(H). In embodiments, R 5 is independently -N(H)C(0)N(CH 3 )(H). In embodiments, R 5 is independently -N(H)C(0)0CH 3 . In embodiments, R 5 is independently -N(H)S(0) 2 CH 3 . In embodiments, R 5 is independently -C(0)CH 3 . In embodiments, R 5 is independently -S(0)CH 3 .
  • R 5 is independently -CH 2 N(H)C(0)CH 3 . In embodiments, R 5 is independently -CH 2 S(0) 2 CH 3 . In embodiments, R 5 is independently and -CH 2 S(0) 2 N(CH 3 )(H).
  • R 5 is independently -CH 3 . In embodiments, R 5 is independently -CF 3 . In embodiments, R 5 is independently -CHF 2 . In embodiments, R 5 is independently -CFH 2 . In embodiments, R 5 is independently ethyl. In embodiments, R 5 is independently propyl. In embodiments, R 5 is independently isopropyl. In embodiments, R 5 is independently butyl. In embodiments, R 5 is independently tert-butyl.
  • R 6 is independently halogen. In embodiments, R 6 is independently R 6 is independently oxo. In embodiments, R 6 is independently -CN. In embodiments, R 6 is independently Ci- 6 alkyl. In embodiments, R 6 is independently C 2-6 alkenyl. In embodiments, R 6 is independently C 2-6 alkynyl. In embodiments, R 6 is independently Ci- 6 haloalkyl. In embodiments, R 6 is independently C 3 -i 2 cycloalkyl. In embodiments, R 6 is independently -CH 2 -C 3 -i 2 cycloalkyl. In embodiments, R 6 is independently Ci-nheterocycloalkyl. In embodiments, R 6 is independently -Cfh-Ci-nheterocycloalkyl. In embodiments, R 6 is independently C6-i2aryl. In embodiments,
  • R 6 is independently -CH 2 -C6-i2aryl. In embodiments, R 6 is independently -Cfh-Ci-nheteroaryl. In embodiments, R 6 is independently Ci-nheteroaryl. In embodiments, R 6 is independently -OR 12 . In embodiments, R 6 is independently -SR 12 . In embodiments, R 6 is independently -N(R 12 )(R 13 ). In embodiments, R 6 is independently -C(0)0R 12 . In embodiments, R 6 is independently -0C(0)N(R 12 )(R 13 ). In embodiments, R 6 is independently - N(R 16 )C(0)N(R 12 )(R 13 ).
  • R 6 is independently -N(R 16 )C(0)0R 15 . In embodiments, R 6 is independently -N(R 16 )S(0) 2 R 15 . In embodiments, R 6 is independently -C(0)R 15 . In embodiments, R 6 is independently -S(0)R 15 . In embodiments, R 6 is independently -0C(0)R 15 . In embodiments, R 6 is independently - C(0)N(R 12 )(R 13 ). In embodiments, R 6 is independently -C(0)C(0)N(R 12 )(R 13 ). In embodiments, R 6 is independently -N(R 16 )C(0)R 15 . In embodiments, R 6 is independently -S/CfhR 15 .
  • R 6 is independently C2-6alkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 6 is independently C2-6alkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 6 is independently Ci- 6 haloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 6 is independently C3- ncycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 6 is independently -CH2-C3- ncycloalkyl optionally substituted with one, two, or three R 20a .
  • R 6 is independently Ci- li heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 6 is independently -CH2-C1- li heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 6 is independently C6-i2aryl optionally substituted with one, two, or three R 20a .
  • R 6 is independently -CH 2 -C6-i2aryl optionally substituted with one, two, or three R 20a .
  • R 6 is independently -Cfh-Ci-nheteroaryl optionally substituted with one, two, or three R 20a .
  • R 6 is independently Ci-nheteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently hydrogen. In select embodiments of the compound, R 1 is independently Ci- 6 alkyl optionally substituted with one, two, or three R 20a . In embodiments of the compound, R 1 is independently methyl optionally substituted with one or two R 20a . In further embodiments of the compound, R 1 is independently methyl. In some embodiments of the compound, R 1 is independently ethyl optionally substituted with one, two, or three R 20a . In embodiments of the compound, R 1 is independently ethyl. In some embodiments of the compound, R 1 is independently propyl optionally substituted with one, two, or three R 20a . In embodiments of the compound, R 1 is independently propyl.
  • R 1 is independently -CH2-C2- dictcrocycloalkyl optionally substituted with one, two, or three R 20a . In some embodiments, R 1 is independently - CH2-(monocyclic C2-8heterocycloalkyl) optionally substituted with one, two, or three R 20a . In some embodiments,
  • R 1 is independently -CH2-(monocyclic C3-5heterocycloalkyl) optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH2-(spirocyclic C2-nheterocycloalkyl) optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH2-(spirocyclic C3-iiheterocycloalkyl) optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH2-(fused C2- li heterocycloalkyl) optionally substituted with one, two, or three R 20a .
  • R 1 is independently - CH2-(spirocyclic Ce-sheterocycloalkyl) optionally substituted with one, two, or three R 20a .
  • R 1 is independently Ci- 6 alkyl.
  • R 1 is independently C2-6alkenyl.
  • R 1 is independently C2- 6alkynyl.
  • R 1 is independently C 3 -iocycloalkyl.
  • R 1 is independently -CH 2 -C 3 - l ocycloalkyl.
  • R 1 is independently C 2-9 heterocycloalkyl.
  • R 1 is independently - CH 2 -C 2-9 heterocycloalkyl.
  • R 1 is independently C6-ioaryl. In embodiments, R 1 is independently - CH 2 -C6-ioaryl. In embodiments, R 1 is independently -CEb-Ci-gheteroaryl. In embodiments, R 1 is independently Ci- gheteroaryl. In embodiments, R 1 is independently Ci-6alkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently C 2-6 alkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently C 2-6 alkynyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C 3 -iocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CH 2 -C 3 -iocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently C 2-9 heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CH 2 -C 2-9 heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently C6-ioaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently - CH 2 -C6-ioaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CH 2 -C 1 - gheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Ci-gheteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Ci-6alkyl. In embodiments, R 1 is independently C 2-6 alkenyl. In embodiments, R 1 is independently C 2-6 alkynyl. In embodiments, R 1 is independently Ci-6haloalkyl. In embodiments, R 1 is independently C 3 -i 2 cycloalkyl. In embodiments, R 1 is independently -CH 2 -C 3 -i 2 cycloalkyl. In embodiments, R 1 is independently Ci-nheterocycloalkyl. In embodiments, R 1 is independently -CH 2 -C 1 - li heterocycloalkyl. In embodiments, R 1 is independently C 6 -i 2 aryl.
  • R 1 is independently -CH 2 -C 6 - naryl. In embodiments, R 1 is independently -CEC-Ci-nheteroaryl. In embodiments, R 1 is independently Ci- nheteroaryl.
  • R 1 is independently Ci-6alkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C 2-6 alkenyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C 2-6 alkynyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Ci-6haloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C 3 -i 2 cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 3 - ncycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Ci- li heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 1 - li heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C 6 -i 2 aryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 6 -i 2 aryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -Qk-Ci-nheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Ci-nheteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Cialkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C 2 alkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C ialky l optionally substituted with one, two, or three R 20a .
  • R 1 is independently Cialkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Cialkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Cealkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C 2 alkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cialkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cialkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Csalkcnyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cealkenyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently C2alkynyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Cialkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cialkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Csalkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cealkynyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cihaloalkyl. In embodiments, R 1 is independently Cihaloalkyl. In embodiments, R 1 is independently Cihaloalkyl. In embodiments, R 1 is independently Cihaloalkyl. In embodiments, R 1 is independently Cihaloalkyl. In embodiments, R 1 is independently Cehaloalkyl. In embodiments, R 1 is independently Cehaloalkyl.
  • R 1 is independently Ci cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cicycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cecycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently C7cycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Ciocyclo
  • R 1 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cdictcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cihctcrocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Ceheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Cvheterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Csheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Cearyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently C-arvl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Csaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Csaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cioaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cnaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently Cearyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Ceheteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently C-hetcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Csheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cihctcroarvl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cioheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently Cnheteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 3 cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C4cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CFF-Cscycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 6 cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C7cycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CFF-Cscycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CFF-Cgcycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CH 2 -Ciocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 2 heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 3 heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C4heterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CFF-Csheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 6 heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CH 2 -C7heterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CFF-Csheterocycloalkyl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CFF-Csiheterocycloalkyl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 6 aryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C7aryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CFF-Csaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C9aryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -Cioaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -Cnaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -Ci 2 aryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 2 heteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C3heteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C4heteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CFF-Csheteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C 6 heteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -C7heteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CFF-Csheteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -Cs>heteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 2 -Cioheteroaryl optionally substituted with one, two, or three R 20a . In embodiments, R 1 is independently -CH 2 -Cnheteroaryl optionally substituted with one, two, or three R 20a .
  • R 1 is independently -CH 3 . In embodiments, R 1 is independently -CF 3 . In embodiments, R 1 is independently -CHF 2 . In embodiments, R 1 is independently -CFH 2 . In embodiments, R 1 is independently ethyl. In embodiments, R 1 is independently propyl. In embodiments, R 1 is independently isopropyl. In embodiments, R 1 is independently butyl. In embodiments, R 1 is independently tert-butyl. [00313] In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 7 p is an integer from 0 to 12;
  • R 7 is p is an integer from 0 to 12;
  • R 7 is
  • R 16 is independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 cycloalkyl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 cycloalkyl are optionally substituted with one, two, or three R 20g .
  • R 16 is independently selected from hydrogen and halogen.
  • R 16 is independently selected from hydrogen and fluoro. In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 16 is hydrogen. In embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 16 is fluoro.
  • R 8 is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, and C 2-9 heterocycloalkyl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, and C 2-9 heterocycloalkyl are optionally substituted with one, two, or three R 20c .
  • R 8 is selected from hydrogen, Ci- 6 alkyl, C 3 -iocycloalkyl, and C 2-9 heterocycloalkyl, wherein Ci- 6 alkyl, C 3 -iocycloalkyl, and C 2-9 heterocycloalkyl are optionally substituted with one, two, or three R 20c independently selected from halogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2 - 6alkynyl, C 3 -iocycloalkyl, and C 2-9 heterocycloalkyl.
  • R 8 is selected from hydrogen, methyl, cyclopropyl, cyclobutyl, and oxetanyl, wherein said methyl, cyclopropyl, cyclobutyl, and oxetanyl are optionally substituted with one, two, or three R 20c independently selected from fluoro, methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 8 is selected from hydrogen, methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 8 is selected from halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2 - gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -N(
  • R 8 is selected from Ci- 6 alkyl, C3-iocycloalkyl, and C2-s>heterocycloalkyl, wherein Ci- 6 alkyl, C3-iocycloalkyl, and C2-s>heterocycloalkyl are optionally substituted with one, two, or three R 20c independently selected from halogen, Ci- 6 alkyl, C2- 6alkenyl, C2-6alkynyl, C3-iocycloalkyl, and C2-9heterocycloalkyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, and oxetanyl, wherein said methyl, cyclopropyl, cyclobutyl, and oxetanyl are optionally substituted with one, two, or three R 20c independently selected from fluoro, methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 8 is selected from methyl, cyclopropyl, cyclobutyl, and oxetanyl.
  • R 3 is hydrogen or CN. In additional embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 3 is hydrogen. In further embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 3 is CN.
  • L 1 is a bond. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, L 1 is selected from a Ci-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, -C(O)-, -NHC(O)-, -C(0)NH-,
  • L 1 is a bond. In embodiments, L 1 is Ci-Cealkyl. In embodiments, L 1 is C2-C6alkenyl. In embodiments, L 1 is C2-C6alkynyl. In embodiments, L 1 is -0-. In embodiments, L 1 is -N(R 14 )-. In embodiments, L 1 is -C(O)-. In embodiments, L 1 is -N(R 14 )C(0)-. In embodiments, L 1 is -C(0)N(R 14 )-. In embodiments, L 1 is -S-. In embodiments, L 1 is -S(0) 2 -. In embodiments, L 1 is -S(O)-.
  • L 1 is -S(0) 2 N(R 14 )-. In embodiments, L 1 is -S(0)N(R 14 )-. In embodiments, L 1 is -N(R 14 )S(0)-. In embodiments, L 1 is -N(R 14 )S(0) 2 -. In embodiments, L 1 is -OCON(R 14 )-. In embodiments, L 1 is - N(R 14 )C(0)0-. In embodiments, L 1 is N(R le ). In embodiments, L 1 is C(0)N(R lc ). In embodiments, L 1 is S(0) 2 N(R 1c ). In embodiments, L 1 is S(0)N(R lc ).
  • L 1 is C(R lf )(R lg )0. In embodiments, L 1 is C(R lf )(R lg )N(R lc ). In embodiments, L 1 is C(R lf )(R lg ). In embodiments, L 1 is -N(H)-. In embodiments, L 1 is -N(H)C(0)-. In embodiments, L 1 is -C(0)N(H)-. In embodiments, L 1 is -S(0) 2 N(H)-. In embodiments, L 1 is -S(0)N(H)-. In embodiments, L 1 is -N(H)S(0)-. In embodiments, L 1 is -N(H)S(0) 2 -.
  • L 1 is -OCON(H)-. In embodiments, L 1 is -N(H)C(0)0-. In embodiments, L 1 is -N(H)-.
  • L 1 is -C(0)N(H)-. In embodiments, L 1 is -S(0) 2 N(H)-. In embodiments, L 1 is - S(0)N(H)-. In embodiments, L 1 is -CH2O-. In embodiments, L 1 is -CH 2 N(H)-. In embodiments, L 1 is -
  • R 19 is a monocyclic ring. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 19 is a bicyclic ring system. In some embodiments of the subject compound, or a pharmaceutically acceptable salt or solvate thereof, R 19 is a polycyclic ring system. In embodiments of the
  • R 19 is: X 6
  • Q 1 , Q 3 , and Q 5 are independently N or C(R ld );
  • Q 4 and Q 6 are independently O, S, C(R la )(R lb ), or N(R lc );
  • X 4 , X 5 , X 6 , X 9 , X 10 , X 11 , and X 12 are independently selected from C(R la ) or N;
  • X 7 and X 8 are independently selected from C(R la ), C(R la )(R lb ), N, or N(R lc ); each R la , R lb , R ld , and R lh are each independently selected from hydrogen, halogen, -CN, CYr, alkyl. CY (Jialoalkyl. CYr, alkenyl. CYr,alkynyl.
  • CYr alkenyl. CYr,alkynyl.
  • C3-iocycloalkyl, C 2 -9heterocycloalkyl, Ce-ioaryl, and Ci-9heteroaryl are optionally substituted with one, two, or three R 201 ; or R la and R lb bonded to the same carbon are joined to form a 3-10 membered heterocycloalkyl ring or a C3-iocycloalkyl ring, wherein the 3-10 membered heterocycloalkyl ring or C3-iocycloalkyl ring are optionally substituted with one, two, or three R 201 ; or two R la bonded to adjacent atoms are joined to form a 3-10 membered heterocycloalkyl ring, a Ce-ioaryl ring, a 5-12 membered heteroaryl ring, or a C3-iocycloalkyl ring, wherein the 3-10 membered heterocycloal
  • CYr alkenyl. CYr,alkynyl. C3-iocycloalkyl, C 2. 9heterocycloalkyl, Ce-ioaryl, Ci-9heteroaryl, wherein CYr, alkyl. CYr, alkenyl. CYr,alkynyl. C3- l ocycloalkyl, C 2-9 heterocycloalkyl, Ce-ioaryl, and Ci- 9 heteroaryl are optionally substituted with one, two, or three R 201 .
  • R 2 is selected from
  • each R 5 is independently selected from:
  • W is C(0), S(0), or S(0) 2 ;
  • V is C(R 16 ) or N;
  • R 10 is -L 7 -R 7 ;
  • V is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • R 7 is a 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl are optionally substituted with one or more R 1 , one or more R 4 , or one or more R 6 ; two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i 2 cycloalkyl, Ci-nheterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl, wherein the C3- i 2 cycloalkyl.
  • Ci-nheterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl are optionally substituted with one, two, or three R 20a ; each R 1 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ci- 6 haloalkyl, C3- i 2 cycloalkyl.
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, G-Galkyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, - S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, - N(R 14 )C(0)0-, and -N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0) 2 R
  • R 17 is -G-R 19 ;
  • L 1 is selected from a bond, G-Galkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc ), and
  • R lc is selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, CV,. ioaryl, and Ci-dictcroarvl. wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 201
  • R 19 is selected from a C3-i2cycloalkyl, C2-nheterocycloalkyl, C6-i2aryl, and C2-i2heteroaryl, wherein the C3- ncycloalkyl, C2-iiheterocycloalkyl, C6-i2aryl, and C2-i2heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3- 6cycloalkyl, C2-9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , - 0C(0)N(R 12 )(R
  • R 16 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2- gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0)
  • R 12a is selected from Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C2- gheterocycloalkyl, -CH2-C2-9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH2-Ci-9heteroaryl, and Ci- gheteroaryl, wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, -CH2-C3-iocycloalkyl, C2- yhctcrocycloalkvl.
  • Ci- gheteroaryl are optionally substituted with one, two, or three R 20d ;
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -CH 2 -C3-iocycloalkyl, C 2. gheterocycloalkyl, -CH 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -Ci-9heteroaryl, and Ci- gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -CH 2 -C3-iocycloalkyl, C 2.
  • gheterocycloalkyl, -CH 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -Ci-9heteroaryl, and Ci- gheteroaryl are optionally substituted with one, two, or three R 20d ;
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0)
  • each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, -CH 2 -C3- 6cycloalkyl, C 2 -9heterocycloalkyl, -CH 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -C I - gheteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2 -9heterocycloalkyl, -CH 2 -C 2 -9heterocycloalkyl
  • Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 20f ; each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , and R 201 are each independently selected from halogen, -CN, Ci- 6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, -CH 2 -C3-6cycloalkyl, C 2 -9heterocycloalkyl, -CH 2 -C 2.
  • each R 22 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2.
  • W is C(O), S(O), or S(0) 2 ;
  • V is C(R 16 ) or N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • Ci-Cealkyl C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or 2 to 4 membered heteroalkylene linker, wherein Ci-Cealkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and 2 to 4 membered heteroalkylene linker are optionally substituted with one, two, or three R 20a ;
  • R 7 is a 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, or 5-12 membered heteroaryl, wherein the 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, or 5-12 membered heteroaryl are optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a C3-i 2 cycloalkyl, Ci-nheterocycl
  • Ci-nheterocycloalkyl, C 6 -i 2 aryl, or Ci-nheteroaryl are optionally substituted with one, two, or three R 20a ; each R 1 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ci- 6 haloalkyl, C3- i 2 cycloalkyl.
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, Ci-Cealkyl, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, - S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, - N(R 14 )C(0)0-, and -N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. dictcrocycloalkyl. C 6 -ioaryl, Ci-yhctcroan l.
  • R 17 is -lA-R 19 ;
  • L 1 is selected from a bond, Ci-Cealkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc ),
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), - C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , - S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12
  • gheterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 201 ; or R lf and R lg are joined to form a 4-7 membered heterocycloalkyl ring or a 4-7 membered cycloalkyl ring, wherein the 4-7 membered heterocycloalkyl ring or 4-7 membered cycloalkyl ring are optionally substituted with one, two, or three R 201 ;
  • R lc is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, CV,- ioaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 201
  • R 19 is selected from a C3-i 2 cycloalkyl, C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl, wherein the C3- i 2 cycloalkyl, C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3- 6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -
  • R 12a is selected from Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -C(R 12c ) 2 -C3-iocycloalkyl, C 2.
  • Ci-9heterocycloalkyl gheterocycloalkyl, -C(R 12c ) 2 -C 2 -9heterocyeloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci-9heteroaryl, and Ci-9heteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -C(R 12c ) 2 -C3-iocycloalkyl, C 2 -9heterocycloalkyl, -C(R 12c ) 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci-9heter
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -C(R 12c ) 2 -C3-iocycloalkyl, C 2.
  • Ci-9heterocycloalkyl gheterocycloalkyl, -C(R 12c ) 2 -C 2 -9heterocyeloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci-9heteroaryl, and Ci-9heteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -C(R 12c ) 2 -C3-iocycloalkyl, C 2 -9heterocycloalkyl, -C(R 12c ) 2 -C 2 -9heterocycloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci-9heter
  • R 12c is independently selected from hydrogen and R 20k ;
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0)
  • Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are optionally substituted with one, two, or three R 20f ; each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 201 , and R 20k are each independently selected from halogen, oxo, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2 - gheterocycloalkyl, C 6 -ioaryl, -CFF-
  • R 7 is a 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl, wherein the 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the a 4- 12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl are optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent
  • W is C(O), S(O), or S(0) 2 ;
  • V is C(R 17 ) and J is C(R 16 ), or V is C(R 17 ) and J is N, or J is C(R 17 ) and V is C(R 16 ), or J is C(R 17 ) and V is N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • Ci-Cealkyl C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or 2 to 4 membered heteroalkylene linker, wherein Ci-Cealkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and 2 to 4 membered heteroalkylene linker are unsubstituted or optionally substituted;
  • R 7 is a 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, or 5-12 membered heteroaryl, wherein the 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, or 5-12 membered heteroaryl are unsubstituted or optionally substituted;
  • R 8 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. dictcrocycloalkyl. C 6 -ioaryl, Ci-dictcroarvl.
  • R 17 is -G-R 19 ;
  • L 1 is selected from a bond, G-Galkyl, C 2 -C 6 alkenyl, C 2 -Galkynyl, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), - C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , - S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12
  • gheterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are unsubstituted or optionally substituted; or R lf and R lg are joined to form a 4-7 membered heterocycloalkyl ring or a 4-7 membered cycloalkyl ring, wherein the 4- 7 membered heterocycloalkyl ring or 4-7 membered cycloalkyl ring are unsubstituted or optionally substituted;
  • R lc is selected from hydrogen, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, G,. loaryl, and Ci- ⁇ j hctcroaiyl. wherein Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C6-ioaryl, and Ci-gheteroaryl are unsubstituted or optionally substituted;
  • R 19 is selected from a C 3 -i 2 cycloalkyl, C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl, wherein the G- ncycloalkyl, C 2 -iiheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl are unsubstituted or optionally substituted;
  • R 16 is selected from hydrogen, halogen, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, G- gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S
  • R 12a is selected from Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -G-iocycloalkyl, G- gheterocycloalkyl, -C(R 12c ) 2 -G- 9 heterocyeloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -G-ioaryl, -C(R 12c ) 2 -G- 9 heteroaryl, and Ci- 9 heteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocycloalkyl, C 6 -
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocyeloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci- 9 heteroaryl, and Ci- 9 heteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2 -C 2-9 hetero
  • R 12c is selected from hydrogen, halogen, oxo, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C6-ioaryl, -CH 2 -C6-ioaryl, -CH 2 -C 1.
  • Ci-sheteroaiyl Ci-sheteroaiyl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(0)0R 22 , -C(0)N(R 22 )(R 23 ), - C(0)C(0)N(R 22 )(R 23 ), -0C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)0R 25 , -N(R 24 )C(0)R 25 , - N(R 24 )S(0) 2 R 25 , -C(0)R 25 , -S(0) 2 R 25 , -S(0) 2 N(R 22 )(R 23 ), -0CH 2 C(0)0R 22 , and -0C(0)R 25 , wherein Ci- 6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycl
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2 - gheterocycloalkyl, C 6 -ioaryl, Ci-dictcroarvl.
  • each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -C 1 - gheteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl,
  • R 7 is a 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl, wherein the 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the a 4- 12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl are optionally substituted or unsubstituted.
  • W is C(O), S(O), or S(0) 2 ;
  • V is C(R 16 ) or N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • Ci-Cealkyl C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or 2 to 4 membered heteroalkylene linker, wherein Ci-Cealkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and 2 to 4 membered heteroalkylene linker are unsubstituted or optionally substituted;
  • R 7 is a 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, or 5-12 membered heteroaryl, wherein the 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the 3-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 6-12 membered aryl, or 5-12 membered heteroaryl are unsubstituted or optionally substituted;
  • R 8 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2. dictcrocycloalkyl. C 6 -ioaryl, Ci-dictcroarvl.
  • R 17 is -G-R 19 ;
  • L 1 is selected from a bond, G-Galkyl, C 2 -C 6 alkenyl, C 2 -Galkynyl, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-6cycloalkyl, C 2 -9heterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), - C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , - S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12
  • gheterocycloalkyl, C 6 -ioaryl, and Ci-gheteroaryl are unsubstituted or optionally substituted; or R lf and R lg are joined to form a 4-7 membered heterocycloalkyl ring or a 4-7 membered cycloalkyl ring, wherein the 4- 7 membered heterocycloalkyl ring or 4-7 membered cycloalkyl ring are unsubstituted or optionally substituted;
  • R lc is selected from hydrogen, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, G,. loaryl, and Ci- ⁇ j hctcroaiyl. wherein Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C6-ioaryl, and Ci-gheteroaryl are unsubstituted or optionally substituted;
  • R 19 is selected from a C 3 -i 2 cycloalkyl, C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl, wherein the G- ncycloalkyl, C 2 -iiheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl are unsubstituted or optionally substituted;
  • R 16 is selected from hydrogen, halogen, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, G- gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S
  • R 12a is selected from Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -G-iocycloalkyl, G- gheterocycloalkyl, -C(R 12c ) 2 -G- 9 heterocyeloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -G-ioaryl, -C(R 12c ) 2 -G- 9 heteroaryl, and Ci- 9 heteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocycloalkyl, C 6 -
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocyeloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci- 9 heteroaryl, and Ci- 9 heteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2 -C 2-9 hetero
  • R 12c is selected from hydrogen, halogen, oxo, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C6-ioaryl, -CH 2 -C6-ioaryl, -CH 2 -C 1.
  • Ci-sheteroaiyl Ci-sheteroaiyl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(0)0R 22 , -C(0)N(R 22 )(R 23 ), - C(0)C(0)N(R 22 )(R 23 ), -0C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)N(R 22 )(R 23 ), -N(R 24 )C(0)0R 25 , -N(R 24 )C(0)R 25 , - N(R 24 )S(0) 2 R 25 , -C(0)R 25 , -S(0) 2 R 25 , -S(0) 2 N(R 22 )(R 23 ), -0CH 2 C(0)0R 22 , and -0C(0)R 25 , wherein Ci- 6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycl
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2 - gheterocycloalkyl, C 6 -ioaryl, Ci-gheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 ,
  • each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl, -CH 2 -C 6 -ioaryl, -CH 2 -C 1 - gheteroaryl, and Ci-gheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, -CH 2 -C 3 - 6cycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -ioaryl,
  • R 7 is a 4- 12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl, wherein the 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the a 4- 12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl are optionally substituted or unsubstituted.
  • V is C(R 17 ) and J is C(R 16 ), or V is C(R 17 ) and J is N, or J is C(R 17 ) and V is C(R 16 ), or J is C(R 17 ) and V is N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • Ci-Cealkyl C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or 2 to 4 membered heteroalkylene linker, wherein Ci-Cealkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and 2 to 4 membered heteroalkylene linker are optionally substituted with one, two, or three R 20a ;
  • R 7 is a 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl, wherein the 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl are optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; wherein two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a 3-12 membered cycloalkyl, 3-12 membered
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, G-Galkyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, - S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, - N(R 14 )C(0)0-, and -N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, C 2 -9heterocycloalkyl, G- i 2 aryl, Ci-nheteroaiyl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), - C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S
  • R 17 is -L ! -R 19 ;
  • L 1 is selected from a bond, Ci-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc ), and C
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, C6-i2aryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), - C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , - S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12
  • R lc is selected from hydrogen, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, naryl, Ci-nheteroaryl, wherein C h alky 1, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, CV,. naryl, and Ci-nheteroaryl are optionally substituted with one, two, or three R 201 ;
  • R 19 is selected from a C3-i2cycloalkyl, C2-nheterocycloalkyl, C6-i2aryl, and C2-i2heteroaryl, wherein the C3- ncycloalkyl, C2-iiheterocycloalkyl, C6-i2aryl, and C2-i2heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, oxo, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3- locycloalkyl, C2-9heterocycloalkyl, Gs-naryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , - 0C(0)N(R 12
  • R 16 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2- gheterocycloalkyl, C6-i2aryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -
  • R 12a is selected from Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocyeloalkyl, C6-ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci- 9 heteroaryl, and Ci-gheteroaryl, wherein Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocycloal
  • R 12b is selected from hydrogen, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocyeloalkyl, C6-ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci- 9 heteroaryl, and Ci-gheteroaryl, wherein Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocycl
  • R 12c is independently selected from hydrogen and R 20k ;
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, C 6 -i 2 aryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15
  • each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -CH 2 -C 3 - locycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -i 2 aryl, -CH 2 -C 6 -i 2 aryl, -CH 2 -C 1 - nheteroaryl, and Ci-nheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -CH 2 -C 3 - locycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C
  • each R 22 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, C 2. dictcrocycloalkyl.
  • C 6 -i 2 aryl, and Ci-nheteroaryl each R 23 is independently selected from H and Ci- 6 alkyl; each R 24 is independently selected from H and Ci- 6 alkyl; each R 25 is independently selected from Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, C 2. siheterocycloalkyl, C 6 -i 2 aryl, and Ci-nheteroaryl; and indicates a single or double bond such that all valences are satisfied.
  • W is C(O), S(O), or S(0) 2 ;
  • V is C(R 16 ) or N;
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(O)-, -S(0) 2 N(R 14 )-, -
  • Ci-Cealkyl C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or 2 to 4 membered heteroalkylene linker, wherein Ci-Cealkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and 2 to 4 membered heteroalkylene linker are optionally substituted with one, two, or three R 20a ;
  • R 7 is a 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl, wherein the 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, and 5-12 membered heteroaryl each comprises one or more ring nitrogen atoms or one or more ring oxygen atoms and wherein the 4-12 membered cycloalkyl, 3-12 membered heterocycloalkyl, 7-12 membered aryl, or 5-12 membered heteroaryl are optionally substituted with one or more R 1 , optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; two substituents selected from R 1 , R 4 , and R 6 that are bonded to the same or adjacent atoms are optionally joined to form a 3-12 membered cycloalkyl, 3-12 membered heterocycl
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond, Ci-Cealkyl, -0-, -N(R 14 )-, -C(O)-, -N(R 14 )C(0)-, -C(0)N(R 14 )-, - S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, -OCON(R 14 )-, - N(R 14 )C(0)0-, and -N(R 14 )C(0)N(R 14 )-; each R 5 is independently hydrogen, or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein;
  • R 8 is selected from halogen, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, i 2 aryl, Ci-nheteroaiyl, -OR 12 , -SR 12 , -N(H)(R 12 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), - C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15 , -S(0) 2 R
  • R 17 is -lA-R 19 ;
  • L 1 is selected from a bond, Ci-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, -0-, -N(R 14 )-, -C(0)-, -N(R 14 )C(0)-, - C(0)N(R 14 )-, -S-, -S(0) 2 -, -S(0)-, -S(0) 2 N(R 14 )-, -S(0)N(R 14 )-, -N(R 14 )S(0)-, -N(R 14 )S(0) 2 -, - OCON(R 14 )-, -N(R 14 )C(0)0-, N(R le ), C(0)N(R lc ), S(0) 2 N(R lc ), S(0)N(R lc ), C(R lf )(R lg )0, C(R lf )(R lg )N(R lc ), and C(R
  • R le , R lf , and R lg are independently selected from hydrogen, halogen, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, Gs-naryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), - C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , - S(0)R 15 , -0C(0)R 15 , -C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12
  • R 19 is selected from a C 3 -i 2 cycloalkyl, C 2 -nheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl, wherein the C 3 - ncycloalkyl, C 2 -iiheterocycloalkyl, C 6 -i 2 aryl, and C 2 -i 2 heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, oxo, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 - locycloalkyl, C 2-9 heterocycloalkyl, C 6 -i 2 aryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12
  • R 16 is selected from hydrogen, halogen, -CN, Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, C 6 -i 2 aryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R 15
  • R 12a is selected from Ci-6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocyeloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci- 9 heteroaryl, and Ci- 9 heteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocycloal
  • R 12b is selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, -C(R 12c ) 2 -C 2-9 heterocyeloalkyl, C 6 -ioaryl, -C(R 12c ) 2 -C 6 -ioaryl, -C(R 12c ) 2 -Ci- 9 heteroaryl, and Ci- 9 heteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -C(R 12c ) 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -C(R 12c ) 2 -C 2-9 hetero
  • R 12c is independently selected from hydrogen and R 20k ;
  • X is C(R 3 ) or N
  • R 3 is selected from hydrogen, halogen, -CN, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, C 2 - gheterocycloalkyl, C 6 -i 2 aryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), - N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14 )S(0) 2 R 15 , -C(0)R 15 , -S(0)R 15 , -0C(0)R 15 , - C(0)N(R 12 )(R 13 ), -C(0)C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)R
  • gheterocycloalkyl, C 6 -i 2 aryl, and Ci-nheteroaryl are optionally substituted with one, two, or three R 20f ; each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 201 , and R 20k is independently selected from halogen, oxo, -CN, G- 6alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C3-iocycloalkyl, -CH 2 -C3-iocycloalkyl, C 2 -9heterocycloalkyl, -CH 2 -C 2.
  • one R 4 is an electrophilic moiety capable of forming a covalent bond with a cysteine, serine, or aspartate residue at an amino acid position corresponding to 12 or 13 of a human KRAS protein;
  • one R 4 is an electrophilic moiety capable of forming a covalent bond with a cysteine, serine, or aspartate residue at an amino acid position corresponding to 12 or 13 of a human KRAS protein;
  • W is C(O); V is C(R 17 ) and J is C(R 16 );
  • R 10 is -L 7 -R 7 ;
  • L 7 is a bond, -0-, or -N(R 14 )-;
  • R 7 is a 3-12 membered heterocycloalkyl, wherein the 3-12 membered heterocycloalkyl comprises one or more ring nitrogen atoms and wherein the 3-12 membered heterocycloalkyl, is optionally substituted with one or more R 4 , and optionally substituted with one or more R 6 ; each R 4 is independently selected from halogen, oxo, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C 2 -9heterocycloalkyl, C 6 -i2aiyl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R
  • naryl, and Ci-nheteroaryl are optionally substituted with one, two, or three R 20a ;
  • one R 4 is optionally independently an electrophilic moiety capable of forming a covalent bond with a cysteine, serine, or aspartate residue at an amino acid position corresponding to 12 or 13 of a human KRAS protein;
  • R 6 is -L 2 -R 5 ; each L 2 is independently selected from a bond and -C(O)-; each R 5 is independently hydrogen or a group other than an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS protein; each R 5 is independently selected from hydrogen, halogen, oxo, -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3- locycloalkyl, C2-9heterocycloalkyl, Gs-naryl, Ci-nheteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , - 0C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)N(R 12 )(R 13 ), -N(R 14 )C(0)0R 15 , -N(R 14
  • R 8 is selected from -CN, Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, C2-9heterocycloalkyl, and -C(0)R 12 , wherein Ci- 6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-iocycloalkyl, and C2-9heterocycloalkyl are optionally substituted with one, two, or three R 20c ;
  • R 17 is -LCR 19 ;
  • L 1 is a bond;
  • R 19 is selected from a C 6 -i 2 aryl and C 2 -i 2 heteroaryl, wherein the C 6 -i 2 aryl and C 2 -i 2 heteroaryl are optionally substituted with one, two, three, four, five, six, or seven R 11 ; each R 11 is independently selected from halogen, oxo, -CN, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 - 6 cycloalkyl, Cz-sheterocycloalkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(0)0R 12 , -C(0)R 12 , -C(0)N(R 12 )(R 13 ), and -N(R 14 )C(0)R 12 , wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6
  • R 16 is selected from hydrogen and halogen
  • R 2 is -0-R 12a ;
  • R 12a is -C(R 12c ) 2 -C 2-9 heterocycloalkyl, wherein -C(R 12c ) 2 -C 2-9 heterocyeloalkyl is optionally substituted with one, two, or three R 20d ;
  • R 12c is independently selected from hydrogen and Ci- 3 alkyl
  • X is C(R 3 ) orN
  • R 3 is selected from hydrogen and -CN; each R 12 is independently selected from hydrogen, Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -CH 2 -C 3 - locycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -i 2 aryl, -CH 2 -C 6 -i 2 aryl, -CH 2 -C 1 - nheteroaryl, and Ci-nheteroaryl, wherein Ci- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -CH 2 -C 3 - locycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2-9 heterocycloalkyl, C 6 -i 2 aryl, -CH 2 -C 6 -
  • each R 20a , R 20c , R 20d , R 20e , R 20f , and R 201 is independently selected from halogen, oxo, -CN, Ci- 6 alkyl, C 2 - 6alkenyl, C 2-6 alkynyl, C 3 -iocycloalkyl, -CH 2 -C 3 -iocycloalkyl, C 2-9 heterocycloalkyl, -CH 2 -C 2 - gheterocycloalkyl, C 6 -i 2 aryl, -CH 2 -C 6

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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  • Steroid Compounds (AREA)
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Abstract

La présente divulgation concerne des composés, certains de leurs sels pharmaceutiquement acceptables et leurs méthodes d'utilisation. Les composés et les méthodes offrent un éventail d'utilités en tant qu'outils de thérapeutique, de diagnostic et de recherche. En particulier, ces compositions et méthodes sont utiles pour réduire la production de signalisation de protéines oncogènes.
EP22740705.3A 2021-06-14 2022-06-13 Composés hétéroaryle fusionnés utiles en tant qu'agents anticancéreux Pending EP4355751A1 (fr)

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WO2023196086A2 (fr) * 2022-04-08 2023-10-12 Mirati Therapeutics, Inc. Polythérapies comprenant un inhibiteur de sos1 et un inhibiteur d'egfr
WO2023196218A2 (fr) * 2022-04-08 2023-10-12 Mirati Therapeutics, Inc. Polythérapies comprenant un inhibiteur de sos1 et un inhibiteur de mek
WO2023215906A1 (fr) * 2022-05-06 2023-11-09 Hangzhou Jijing Pharmaceuticaltechnology Limited Chimères ciblant la protéolyse kras g12d
WO2023240263A1 (fr) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Inhibiteurs de ras macrocycliques
WO2024031088A1 (fr) 2022-08-05 2024-02-08 Kumquat Biosciences Inc. Composés hétérocycliques et leurs utilisations
WO2024152247A1 (fr) * 2023-01-18 2024-07-25 Nikang Therapeutics , Inc. Composés bifonctionnels pour la dégradation de kras g12d par l'intermédiaire de la voie ubiquitine-protéasome
WO2024112654A1 (fr) 2022-11-21 2024-05-30 Treeline Biosciences, Inc. Inhibiteurs de kras spirocycliques de dihydropyranopyrimidine
WO2024206858A1 (fr) 2023-03-30 2024-10-03 Revolution Medicines, Inc. Compositions pour induire une hydrolyse de ras gtp et leurs utilisations
WO2024211712A1 (fr) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Composés macrocycliques condensés en tant qu'inhibiteurs de ras
WO2024211663A1 (fr) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Composés macrocycliques condensés en tant qu'inhibiteurs de ras
US20240352036A1 (en) 2023-04-14 2024-10-24 Revolution Medicines, Inc. Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof
US20240352038A1 (en) 2023-04-14 2024-10-24 Revolution Medicines, Inc. Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof

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