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EP-4735445-A1 - KRAS MODULATING COMPOUNDS

EP4735445A1EP 4735445 A1EP4735445 A1EP 4735445A1EP-4735445-A1

Abstract

Provided herein are compounds, and pharmaceutically acceptable salts thereof, useful as KRAS inhibitors, methods of making and using the same (singly or in combination with additional agents), and pharmaceutical compositions thereof.

Inventors

  • DAI, Chaodi
  • MACHICAO TELLO, Paulo A.
  • MACK, James B.C.
  • MCAULEY, Erik P.
  • MCKINLEY, Jessica L.
  • MEDLEY, Jonathan William
  • PYUN, HYUNG-JUNG
  • STRATTON, Thomas P.
  • TIAN, Maoqun
  • TUCK, Jeremy R.
  • WATKINS, WILLIAM J.
  • FARAND, JULIE
  • XU, JIE
  • ZHANG, JENNIFER R.
  • GUERRERO, JUAN A.
  • GUNEY, Tezcan
  • GUO, HONGYAN
  • HUDLICKY, Jason R.
  • KATO, DARRYL
  • KIBURU, Irene N.
  • LAZERWITH, SCOTT E.

Assignees

  • GILEAD SCIENCES, INC.

Dates

Publication Date
20260506
Application Date
20240627

Claims (20)

  1. CLAIMS 1. A compound of Formula (J): or a pharmaceutically acceptable salt thereof, wherein X is N, CH, or CR x ; R x is (CH 2 ) m CN or halo; m is 0, 1, 2 or 3; each R 1 and R 2 is independently H or F, wherein at least one of R 1 and R 2 is F; each R 3 , R 4 , and R 5 is independently H or C 1 -C 3 alkyl; L 1 is O, S, CR 1a R 1b , C(=CR 1c R 1d ), C(=O), or -C(R 1e )=; R 1a and R 1b are each independently H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, -OH, -CN, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 1a and R 1b can combine with the atom to which they are attached to form a C 3 -C 6 cycloalkyl or a 3 to 6 membered heterocyclyl having 1 heteroatom that is O, wherein each cycloalkyl and heterocyclyl is substituted with 0, 1, 2, or 3 R 1x ; R 1c and R 1d are each independently H, C 1 -C 3 alkyl, halo, or C 1 -C 6 haloalkyl; R 1e is H, C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; each R 1x is independently C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or -OH; L 2 is a bond, O, S, CR 2a R 2b , C(=CR 2c R 2d ), C(=O), or =C(R 2e )-, such that when L 2 is O or S, then L 1 is CR 1a R 1b ; R 2a and R 2b are each independently H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, -OH, -CN, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 2a and R 2b can combine with the atom to which they are attached to form a C 3 -C 6 cycloalkyl; alternatively, R 1b and R 2b can combine with the atoms to which they are attached to form a C 3 -C 6 cycloalkyl, 4- to 10-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 14-membered heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl and heteroaryl is substituted with 0, 1, 2, or 3 R 2x ; R 2c and R 2d are each independently H, C 1 -C 3 alkyl, halo, or C 1 -C 6 haloalkyl; R 2e is H, C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 1e and R 2e can combine with the atoms to which they are attached to form a C5-C 6 cycloalkyl, 5- to 10-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 14-membered heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl and heteroaryl is substituted with 0, 1, 2, or 3 R 2x ; each R 2x is independently C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or -OH; alternatively L 1 and L 2 can combine to form L 3 is a bond, CR 3a R 3b , C(=CR 3c R 3d ), C(=O), or =C(R 3e )-; R 3a and R 3b are each independently H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, -OH, -CN, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 3a and R 3b can combine with the atom to which they are attached to form a C 3 -C 6 cycloalkyl; alternatively, R 2b and R 3b can combine with the atoms to which they are attached to form a C 3 -C 6 cycloalkyl; R 3c and R 3d are each independently H, C 1 -C 3 alkyl, halo, or C 1 -C 6 haloalkyl; R 3e is H, C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 2e and R 3e can combine with the atoms to which they are attached to form a C5-C 6 cycloalkyl, 5- to 10-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 14-membered heteroaryl; L 4 is a bond, CR 4a R 4b , C(=CR 4c R 4d ), C(=O), or =C(R 4e )-; R 4a and R 4b are each independently H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, -OH, -CN,C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 4a and R 4b can combine with the atom to which they are attached to form a C 3 -C 6 cycloalkyl; alternatively, R 3b and R 4b can combine with the atoms to which they are attached to form a C 3 -C 6 cycloalkyl; R 4c and R 4d are each independently H, C 1 -C 3 alkyl, halo, or C 1 -C 6 haloalkyl; R 4e is H, C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 3e and R 4e can combine with the atoms to which they are attached to form a C 5 -C 6 cycloalkyl; such that when L 2 is =C(R 2e )- then L 1 is –C(R 1e )= or L 3 is =C(R 3e )-, and when L 3 is =C(R 3e )- then L 2 is =C(R 2e )- or L 4 is =C(R 4e )-; R A is phenyl, naphthyl, or 5- to 14-membered heteroaryl, wherein R A is substituted with 0, 1, 2, 3, 4, or 5 R A2 ; each R A2 is independently -OH, C 1 -C 10 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 10 alkoxy, C 1 -C 10 hydroxyalkyl, C 2 -C 10 alkoxyalkyl, C 1 -C 6 alkyl-N(R A2a )(R A2b ), C 1 -C 10 thioalkyl, halo, C 1 - C 6 haloalkyl, -CN, -C(O)R A2a , -C(O)OR A2a , -OC(O)R A2a , -OC(O)OR A2a , -C(O)N(R A2a )(R A2b ), - N(R A2a )C(O)(R A2b ), -OC(O)N(R A2a )(R A2b ), -N(R A2a )C(O)(OR A2b ), oxo, -OR A2a , -SR A2a , - S(O) 2 R A2a , -S(O) 2 OR A2a , -N(R A2a )(R A2b ), -(C 0 -C 3 alkyl)-SF 5 , -OP(O)(OR A2a )(OR A2b ), C 3 -C 8 cycloalkyl, -(C 1 -C 6 alkyl)-(C 3 -C 8 cycloalkyl), 3- to 14-membered heterocyclyl, -(C 1 -C 6 alkyl)-(3- to 14-membered heterocyclyl), C 6 -C 1 4 aryl, -(C 1 -C 6 alkyl)-(C 6 -C 1 4 aryl), 5- to 14-membered heteroaryl, or -(C 1 -C 6 alkyl)-(5- to 14-membered heteroaryl), wherein each alkyl, alkenyl, alkynyl, alkoxy, hydroxyalkyl, and haloalkyl is substituted with 0, 1, 2, or 3 R A3 , and wherein each cycloalkyl, alkyl-cycloalkyl, heterocyclyl, alkyl-heterocyclyl, aryl, alkyl-aryl, heteroaryl, and alkyl-heteroaryl is substituted with 0, 1, 2, or 3 R A4 ; each R A2a and R A2b is independently H, C 1 -C 10 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 8 cycloalkyl; each R A3 is independently halo, -CN, -OR A3a , -SR A3a , -N(R A3a )(R A3b ), C 3 -C 8 cycloalkyl, or 5- to 14-membered heteroaryl; each R A3a and R A3b is independently H, C 1 -C 10 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 8 cycloalkyl; each R A4 is independently C 1 -C 6 alkoxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkoxyalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkylthio, C 3 -C 8 cycloalkyl, -(C 1 -C 6 alkyl)-(C 6 -C 10 aryl), halo, -CN, -OH, or -N(R A4a )(R A4b ); each R A4a and R A4b is independently H or C 1 -C 6 alkyl; alternatively, two R A2 can combine to form a C 3 -C 10 cycloalkyl, C 6 -C 10 aryl, a 3- to 10-membered heterocyclyl, or 5- to 14-membered heteroaryl on two adjacent atoms on R A , wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is substituted with 0, 1, 2, or 3 R A5 ; each R A5 is independently C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halo, C 1 -C 6 haloalkyl, - CN, or C 3 -C 8 cycloalkyl; R B is H; L C is a bond or Y is C or Si; n is 0, 1, 2, or 3; q is 0, 1, 2, or 3; R Y1 is H or C 1 -C 3 alkyl; R Y2 is H or C 1 -C 3 alkyl; alternatively, R Y1 and R Y2 combine to form a C 3 -C 10 cycloalkyl or a 3- to 10-membered heterocyclyl; R C is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkoxyalkyl, C 1 -C 6 haloalkyl, C 1 - C 6 haloalkoxy, -NH2, -NHR C1 , -N(R C1 )2, C 3 -C 8 cycloalkyl, 3- to 14-membered heterocyclyl, C 6 - C 14 aryl, or 5- to 14-membered heteroaryl, wherein each C 3 -C 8 cycloalkyl, 3- to 14-membered heterocyclyl, C 6 -C 1 4 aryl, and 5- to 14-membered heteroaryl is substituted with 0, 1, 2, 3, or 4 R C3 ; each R C1 is independently selected from C 1 -C 6 alkyl; each R C3 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 8 alkynyl, C 1 -C 6 alkoxyalkyl, C 1 -C 6 hydroxyalkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, -(C 1 -C 6 alkyl)-N(R C3a )(R C3b ), -CN, - C(O)R C3a , -C(O)OR C3a , -C(O)N(R C3a )(R C3b ), -N(R C3a )C(O)(R C3b ), -OC(O)N(R C3a )(R C3b ), -N(R C3a )C(O)(OR C3b ), =CH 2 , =CHF, =CF 2 , oxo, - OR C3a , -SR C3a , -N(R C3a )(R C3b ) , -N 3 , SF 5 , C 3 -C 8 cycloalkyl, -(C 1 -C 6 alkyl)-(C 3 -C 8 cycloalkyl), 3- to 10-membered heterocyclyl, -(C 1 -C 6 alkyl)-(3- to 10-membered heterocyclyl), C 6 -C 10 aryl, -(C 1 - C 6 alkyl)-(C 6 -C 10 aryl), 5- to 10-membered heteroaryl, or -(C 1 -C 6 alkyl)-(5- to 10-membered heteroaryl), wherein each alkyl is substituted with 0, 1, 2, or 3 -CN, -C(O)OR C3a1 , -C(O)N(R C3a1 )(R C3a2 ), -N(R C3a1 )C(O)(R C3a2 ), -OC(O)N(R C3a1 )(R C3a2 ), -OR C3a1 , -SR C3a1 , N3, SF5, or 3- to 10-membered heterocyclyl substituted with 0, 1, 2, or 3 R C3a2 , each cycloalkyl, alkyl-cycloalkyl, heterocyclyl, alkyl-heterocyclyl, aryl, alkyl-aryl, heteroaryl, and alkyl-heteroaryl is substituted with 0, 1, 2, or 3 halo, -CN, or R C3a2 , each alkenyl is substituted with 0, 1, 2, or 3 halo, and each alkoxyalkyl and alkynyl is substituted with 0, 1, 2, or 3 C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl substituted with 0 or 1 C 1 -C 6 haloalkyl, C 6 -C 10 aryl, or 5- to 10-membered heteroaryl; each R C3a and R C3b is independently H, C 1 -C 10 alkyl, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, C 3 -C 6 cycloalkyl, 3- to 6-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each aryl and heteroaryl is substituted with 0, 1, 2, or 3 halo, -CN, or R C3a2 ; alternatively, R C3a and R C3b together with the N to which they are attached form a 3- to 8- membered heterocycle; each R C3a1 and R C3a2 is independently C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, -(C 1 - C 3 alkyl)-(C 3 -C 8 cycloalkyl), 3- to 10-membered heterocyclyl, -(C 1 -C 3 alkyl)-(3- to 10-membered heterocyclyl), C 6 -C 10 aryl, -(C 1 -C 3 alkyl)-(C 6 -C 10 aryl), -(C 2 -C 4 alkynyl)-(C 6 -C 10 aryl), 5- to 10- membered heteroaryl, -(C 1 -C 3 alkyl)-(5- to 10-membered heteroaryl), or SF5, wherein each cycloalkyl, alkyl-cycloalkyl, heterocyclyl, alkyl-heterocyclyl, aryl, alkyl-aryl, alkynyl-aryl, heteroaryl, and alkyl-heteroaryl is substituted with 0, 1, 2, or 3 halo, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, or SF5; alternatively, R C3a1 and R C3a2 together with the N to which they are attached form a 3- to 8- membered heterocycle; R D is halo; each heterocyclyl has 1, 2, 3, or 4 heteroatoms selected from N, O, S, and Si; and each heteroaryl has 1, 2, 3, or 4 heteroatoms selected from N, O, and S. 2. The compound of claim 1, which is a compound of Formula (J): or a pharmaceutically acceptable salt thereof, wherein X is N, CH, or CR x ; R x is (CH 2 ) m CN or halo; m is 0, 1, 2 or 3; each R 1 and R 2 is independently H or F, wherein at least one of R 1 and R 2 is F; each R 3 , R 4 , and R 5 is independently H or C 1 -C 3 alkyl; L 1 is O, S, CR 1a R 1b , C(=CR 1c R 1d ), C(=O), or -C(R 1e )=; R 1a and R 1b are each independently H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, -OH, -CN, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 1a and R 1b can combine with the atom to which they are attached to form a C 3 -C 6 cycloalkyl or a 3 to 6 membered heterocyclyl having 1 heteroatom that is O, wherein each cycloalkyl and heterocyclyl is substituted with 0, 1, 2, or 3 R 1x ; R 1c and R 1d are each independently H, C 1 -C 3 alkyl, halo, or C 1 -C 6 haloalkyl; R 1e is H, C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; each R 1x is independently C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or -OH; L 2 is a bond, O, S, CR 2a R 2b , C(=CR 2c R 2d ), C(=O), or =C(R 2e )-, such that when L 2 is O or S, then L 1 is CR 1a R 1b ; R 2a and R 2b are each independently H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, -OH, -CN, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 2a and R 2b can combine with the atom to which they are attached to form a C 3 -C 6 cycloalkyl; alternatively, R 1b and R 2b can combine with the atoms to which they are attached to form a C 3 -C 6 cycloalkyl, 4- to 10-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 14-membered heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl and heteroaryl is substituted with 0, 1, 2, or 3 R 2x ; R 2c and R 2d are each independently H, C 1 -C 3 alkyl, halo, or C 1 -C 6 haloalkyl; R 2e is H, C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 1e and R 2e can combine with the atoms to which they are attached to form a C 5 -C 6 cycloalkyl, 5- to 10-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 14-membered heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl and heteroaryl is substituted with 0, 1, 2, or 3 R 2x ; each R 2x is independently C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or -OH; alternatively L 1 and L 2 can combine to form L 3 is a bond, CR 3a R 3b , C(=CR 3c R 3d ), C(=O), or =C(R 3e )-; R 3a and R 3b are each independently H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, -OH, -CN, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 3a and R 3b can combine with the atom to which they are attached to form a C 3 -C 6 cycloalkyl; alternatively, R 2b and R 3b can combine with the atoms to which they are attached to form a C 3 -C 6 cycloalkyl; R 3c and R 3d are each independently H, C 1 -C 3 alkyl, halo, or C 1 -C 6 haloalkyl; R 3e is H, C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 2e and R 3e can combine with the atoms to which they are attached to form a C5-C 6 cycloalkyl, 5- to 10-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 14-membered heteroaryl; L 4 is a bond, CR 4a R 4b , C(=CR 4c R 4d ), C(=O), or =C(R 4e )-; R 4a and R 4b are each independently H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, -OH, -CN,C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 4a and R 4b can combine with the atom to which they are attached to form a C 3 -C 6 cycloalkyl; alternatively, R 3b and R 4b can combine with the atoms to which they are attached to form a C 3 -C 6 cycloalkyl; R 4c and R 4d are each independently H, C 1 -C 3 alkyl, halo, or C 1 -C 6 haloalkyl; R 4e is H, C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 3 cyanoalkyl, or C 3 -C 6 cycloalkyl; alternatively, R 3e and R 4e can combine with the atoms to which they are attached to form a C 5 -C 6 cycloalkyl; such that when L 2 is =C(R 2e )- then L 1 is –C(R 1e )= or L 3 is =C(R 3e )-, and when L 3 is =C(R 3e )- then L 2 is =C(R 2e )- or L 4 is =C(R 4e )-; R A is phenyl, naphthyl, or 5- to 14-membered heteroaryl, wherein R A is substituted with 0, 1,
  2. 2,
  3. 3,
  4. 4, or 5 R A2 ; each R A2 is independently -OH, C 1 -C 10 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 10 alkoxy, C 1 -C 10 hydroxyalkyl, C 2 -C 10 alkoxyalkyl, C 1 -C 6 alkyl-N(R A2a )(R A2b ), C 1 -C 10 thioalkyl, halo, C 1 - C 6 haloalkyl, -CN, -C(O)R A2a , -C(O)OR A2a , -OC(O)R A2a , -OC(O)OR A2a , -C(O)N(R A2a )(R A2b ), - N(R A2a )C(O)(R A2b ), -OC(O)N(R A2a )(R A2b ), -N(R A2a )C(O)(OR A2b ), oxo, -OR A2a , -SR A2a , - S(O) 2 R A2a , -S(O) 2 OR A2a , -N(R A2a )(R A2b ), -(C 0 -C 3 alkyl)-SF 5 , -OP(O)(OR A2a )(OR A2b ), C 3 -C 8 cycloalkyl, -(C 1 -C 6 alkyl)-(C 3 -C 8 cycloalkyl), 3- to 14-membered heterocyclyl, -(C 1 -C 6 alkyl)-(3- to 14-membered heterocyclyl), C 6 -C 1 4 aryl, -(C 1 -C 6 alkyl)-(C 6 -C 1 4 aryl), 5- to 14-membered heteroaryl, or -(C 1 -C 6 alkyl)-(5- to 14-membered heteroaryl), wherein each alkyl, alkenyl, alkynyl, alkoxy, hydroxyalkyl, and haloalkyl is substituted with 0, 1, 2, or 3 R A3 , and wherein each cycloalkyl, alkyl-cycloalkyl, heterocyclyl, alkyl-heterocyclyl, aryl, alkyl-aryl, heteroaryl, and alkyl-heteroaryl is substituted with 0, 1, 2, or 3 R A4 ; each R A2a and R A2b is independently H, C 1 -C 10 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 8 cycloalkyl; each R A3 is independently halo, -CN, -OR A3a , -SR A3a , -N(R A3a )(R A3b ), C 3 -C 8 cycloalkyl, or 5- to 14-membered heteroaryl; each R A3a and R A3b is independently H, C 1 -C 10 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 8 cycloalkyl; each R A4 is independently C 1 -C 6 alkoxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkoxyalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkylthio, C 3 -C 8 cycloalkyl, -(C 1 -C 6 alkyl)-(C 6 -C 10 aryl), halo, -CN, -OH, or -N(R A4a )(R A4b ); each R A4a and R A4b is independently H or C 1 -C 6 alkyl; alternatively, two R A2 can combine to form a C 3 -C 10 cycloalkyl, C 6 -C 10 aryl, a 3- to 10-membered heterocyclyl, or 5- to 14-membered heteroaryl on two adjacent atoms on R A , wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is substituted with 0, 1, 2, or 3 R A5 ; each R A5 is independently C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halo, C 1 -C 6 haloalkyl, - CN, or C 3 -C 8 cycloalkyl; R B is H; L C is a bond or Y is C or Si; n is 0, 1, 2, or 3; q is 0, 1, 2, or 3; R Y1 is H or C 1 -C 3 alkyl; R Y2 is H or C 1 -C 3 alkyl; alternatively, R Y1 and R Y2 combine to form a C 3 -C 10 cycloalkyl or a 3- to 10-membered heterocyclyl; R C is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkoxyalkyl, C 1 -C 6 haloalkyl, C 1 - C 6 haloalkoxy, -NH2, -NHR C1 , -N(R C1 )2, C 3 -C 8 cycloalkyl, 3- to 14-membered heterocyclyl, C 6 - C 1 4 aryl, or 5- to 14-membered heteroaryl, wherein each C 3 -C 8 cycloalkyl, 3- to 14-membered heterocyclyl, C 6 -C 14 aryl, and 5- to 14-membered heteroaryl is substituted with 0, 1, 2, 3, or 4 R C3 ; each R C1 is independently selected from C 1 -C 6 alkyl; each R C3 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 8 alkynyl, C 1 -C 6 alkoxyalkyl, C 1 -C 6 hydroxyalkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, -(C 1 -C 6 alkyl)-N(R C3a )(R C3b ), -CN, - C(O)R C3a , -C(O)OR C3a , -C(O)N(R C3a )(R C3b ), -N(R C3a )C(O)(R C3b ), -OC(O)N(R C3a )(R C3b ), -N(R C3a )C(O)(OR C3b ), =CH 2 , =CF 2 , oxo, -OR C3a , - SR C3a , -N(R C3a )(R C3b ) , -N 3 , SF 5 , C 3 -C 8 cycloalkyl, -(C 1 -C 6 alkyl)-(C 3 -C 8 cycloalkyl), 3- to 10- membered heterocyclyl, -(C 1 -C 6 alkyl)-(3- to 10-membered heterocyclyl), C 6 -C 10 aryl, -(C 1 -C 6 alkyl)-(C 6 -C 10 aryl), 5- to 10-membered heteroaryl, or -(C 1 -C 6 alkyl)-(5- to 10-membered heteroaryl), wherein each alkyl is substituted with 0, 1, 2, or 3 -CN, -C(O)OR C3a1 , -C(O)N(R C3a1 )(R C3a2 ), -N(R C3a1 )C(O)(R C3a2 ), -OC(O)N(R C3a1 )(R C3a2 ), -OR C3a1 , -SR C3a1 , N3, SF5, or 3- to 10-membered heterocyclyl substituted with 0, 1, 2, or 3 R C3a2 , each cycloalkyl, alkyl-cycloalkyl, heterocyclyl, alkyl-heterocyclyl, aryl, alkyl-aryl, heteroaryl, and alkyl-heteroaryl is substituted with 0, 1, 2, or 3 halo, -CN, or R C3a2 , each alkenyl is substituted with 0, 1, 2, or 3 halo, and each alkoxyalkyl and alkynyl is substituted with 0, 1, 2, or 3 C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl substituted with 0 or 1 C 1 -C 6 haloalkyl, C 6 -C 10 aryl, or 5- to 10-membered heteroaryl; each R C3a and R C3b is independently H, C 1 -C 10 alkyl, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, C 3 -C 6 cycloalkyl, 3- to 6-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each aryl and heteroaryl is substituted with 0, 1, 2, or 3 halo, -CN, or R C3a2 ; alternatively, R C3a and R C3b together with the N to which they are attached form a 3- to 8- membered heterocycle; each R C3a1 and R C3a2 is independently C 1 -C 3 alkyl, halo, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, -(C 1 - C 3 alkyl)-(C 3 -C 8 cycloalkyl), 3- to 10-membered heterocyclyl, -(C 1 -C 3 alkyl)-(3- to 10-membered heterocyclyl), C 6 -C 10 aryl, -(C 1 -C 3 alkyl)-(C 6 -C 10 aryl), -(C 2 -C 4 alkynyl)-(C 6 -C 10 aryl),
  5. 5- to 10- membered heteroaryl, -(C 1 -C 3 alkyl)-(5- to 10-membered heteroaryl), or SF 5 , wherein each cycloalkyl, alkyl-cycloalkyl, heterocyclyl, alkyl-heterocyclyl, aryl, alkyl-aryl, alkynyl-aryl, heteroaryl, and alkyl-heteroaryl is substituted with 0, 1, 2, or 3 halo, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, or SF5; alternatively, R C3a1 and R C3a2 together with the N to which they are attached form a 3- to 8- membered heterocycle; R D is halo; each heterocyclyl has 1, 2, 3, or 4 heteroatoms selected from N, O, S, and Si; and each heteroaryl has 1, 2, 3, or 4 heteroatoms selected from N, O, and S. 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are each H. 4. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, having the structure of Formula (I): 5. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, having the structure of Formula (I-1):
  6. 6. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, having the structure of Formula (I-2):
  7. 7. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, having the structure of Formula (I-3):
  8. 8. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein X is N.
  9. 9. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein X is CH.
  10. 10. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein X is C-Cl.
  11. 11. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein L 1 is O.
  12. 12. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein R 5 is H.
  13. 13. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, having the structure of Formula (II):
  14. 14. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, having the structure of Formula (IIa):
  15. 15. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein L 1 is O, S, or CR 1a R 1b .
  16. 16. The compound of any one of claims 1 to 13 and 15, or a pharmaceutically acceptable salt thereof, wherein L 1 is CHR 1b .
  17. 17. The compound of any one of claims 1 to 13 and 15 to 16, or a pharmaceutically acceptable salt thereof, wherein R 1a and R 1b are each independently H, C 1 -C 3 alkyl, or halo.
  18. 18. The compound of any one of claims 1 to 13 and 15 to 17, or a pharmaceutically acceptable salt thereof, wherein R 1b is C 1 -C 3 alkyl or halo.
  19. 19. The compound of any one of claims 1 to 13 and 15 to 18, or a pharmaceutically acceptable salt thereof, wherein R 1b is methyl.
  20. 20. The compound of any one of claims 1 to 13 and 15 to 17, or a pharmaceutically acceptable salt thereof, wherein L 1 is CH 2 .

Description

KRAS MODULATING COMPOUNDS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 63/511,496, filed on June 30, 2023, and U.S. Provisional Application No. 63/553,004, filed on February 13, 2024, each of which is incorporated herein by reference in its entirety for all purposes. BACKGROUND [0002] The KRAS protein, Kirsten Rat Sarcoma 2 Viral Oncogene Homolog (“KRAS”), is a GTPase. KRAS gene mutations have been observed in a number of conditions including, for instance, pancreatic cancer, endometrial cancer, lung adenocarcinoma, colorectal cancer, rectal carcinoma, gall bladder cancer, thyroid cancer, bile duct cancer, small cell lung cancer, and non- small cell lung cancer (NSCLC). Accordingly, there is a need for compounds, pharmaceutical compositions, and methods for inhibiting KRAS (e.g., wild type, KRAS G12C, KRAS G12D, and/or KRAS G12V) and treating associated cancers. SUMMARY [0003] In one embodiment, the present disclosure provides a compound of Formula J: or a pharmaceutically acceptable salt thereof, wherein X is N, CH, or CRx; Rx is (CH2)mCN or halo; m is 0, 1, 2 or 3; each R1 and R2 is independently H or F, wherein at least one of R1 and R2 is F; each R3, R4, and R5 is independently H or C1-C3 alkyl; L1 is O, S, CR1aR1b, C(=CR1cR1d), C(=O), or -C(R1e)=; R1a and R1b are each independently H, C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, -OH, -CN, C1-C3 cyanoalkyl, or C3-C6 cycloalkyl; alternatively, R1a and R1b can combine with the atom to which they are attached to form a C3-C6 cycloalkyl or a 3 to 6 membered heterocyclyl having 1 heteroatom that is O, wherein each cycloalkyl and heterocyclyl is substituted with 0, 1, 2, or 3 R1x; R1c and R1d are each independently H, C1-C3 alkyl, halo, or C1-C6 haloalkyl; R1e is H, C1-C3 alkyl, halo, C1-C6 haloalkyl, C1-C3 cyanoalkyl, or C3-C6 cycloalkyl; each R1x is independently C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, or -OH; L2 is a bond, O, S, CR2aR2b, C(=CR2cR2d), C(=O), or =C(R2e)-, such that when L2 is O or S, then L1 is CR1aR1b; R2a and R2b are each independently H, C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, -OH, -CN, C1-C3 cyanoalkyl, or C3-C6 cycloalkyl; alternatively, R2a and R2b can combine with the atom to which they are attached to form a C3-C6 cycloalkyl; alternatively, R1b and R2b can combine with the atoms to which they are attached to form a C3-C6 cycloalkyl, 4- to 10-membered heterocyclyl, C6-C10 aryl, or 5- to 14-membered heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl and heteroaryl is substituted with 0, 1, 2, or 3 R2x; R2c and R2d are each independently H, C1-C3 alkyl, halo, or C1-C6 haloalkyl; R2e is H, C1-C3 alkyl, halo, C1-C6 haloalkyl, C1-C3 cyanoalkyl, or C3-C6 cycloalkyl; alternatively, R1e and R2e can combine with the atoms to which they are attached to form a C5-C6 cycloalkyl, 5- to 10-membered heterocyclyl, C6-C10 aryl, or 5- to 14-membered heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl and heteroaryl is substituted with 0, 1, 2, or 3 R2x; each R2x is independently C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, or -OH; alternatively L1 and L2 can combine to form L3 is a bond, CR3aR3b, C(=CR3cR3d), C(=O), or =C(R3e)-; R3a and R3b are each independently H, C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, -OH, -CN, C1-C3 cyanoalkyl, or C3-C6 cycloalkyl; alternatively, R3a and R3b can combine with the atom to which they are attached to form a C3-C6 cycloalkyl; alternatively, R2b and R3b can combine with the atoms to which they are attached to form a C3-C6 cycloalkyl; R3c and R3d are each independently H, C1-C3 alkyl, halo, or C1-C6 haloalkyl; R3e is H, C1-C3 alkyl, halo, C1-C6 haloalkyl, C1-C3 cyanoalkyl, or C3-C6 cycloalkyl; alternatively, R2e and R3e can combine with the atoms to which they are attached to form a C5-C6 cycloalkyl, 5- to 10-membered heterocyclyl, C6-C10 aryl, or 5- to 14-membered heteroaryl; L4 is a bond, CR4aR4b, C(=CR4cR4d), C(=O), or =C(R4e)-; R4a and R4b are each independently H, C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C6 haloalkyl, C1-C6 haloalkoxy, -OH, -CN,C1-C3 cyanoalkyl, or C3-C6 cycloalkyl; alternatively, R4a and R4b can combine with the atom to which they are attached to form a C3-C6 cycloalkyl; alternatively, R3b and R4b can combine with the atoms to which they are attached to form a C3-C6 cycloalkyl; R4c and R4d are each independently H, C1-C3 alkyl, halo, or C1-C6 haloalkyl; R4e is H, C1-C3 alkyl, halo, C1-C6 haloalkyl, C1-C3 cyanoalkyl, or C3-C6 cycloalkyl; alternatively, R3e and R4e can combine with the atoms to which they are attached to form a C5-C6 cycloalkyl; such that when L2 is =C(R2e)- then L1 is –C(R1e)= or L3 is =C(R3e)-, and when L3 is =C(R3e)- then L2 is =C(R2e)- or L4 is =C(R4e)-; RA is phenyl, naphthyl, or 5- to 14-membered heteroaryl, wherein RA is substituted wit