Cbl-b inhibitors and methods of use thereof

A compound having a structure according to Formula II:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• ring A is selected from the group consisting of:
• R1, when present, is —H or C1-C3 alkyl;
• R2, when present, is H;
• —CN;
• —NR2aR2b, wherein R2a and R2b are independently selected from H and C1-C6 alkyl;
• —S(O)2(C1-C3 alkyl);
• —S(O)(NR2c)(C1-C3 alkyl);
• —NR2c—S(O)2(C1-C3 alkyl);
• —S(O)2—N(R2c)2;
• 5- to 6-membered heteroaryl containing 1-3 ring heteroatoms independently selected from N, S, and O, and the 5- or 6-membered heteroaryl is substituted with 0-3 C1-C3 alkyl;
• 5- or 6-membered heterocycloalkyl ring having 1-2 ring heteroatoms independently selected from N, S, and O, and the 5- or 6-membered heterocycloalkyl ring is substituted with 0-3 C1-C3 alkyl;
• unsubstituted C1-C3 alkyl;
• or C1-C3 alkyl substituted with (i) —OR2c, (ii) —C(O)NRaRb, (iii) —NRaRb, (iv) a 4- to 8-membered heterocycloalkyl ring having 1-2 ring heteroatoms independently selected from N, S, and O, and the 4- to 8-membered heterocycloalkyl ring is substituted with 0-3 substituents independently selected from halo, —OH, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 hydroxyalkyl, or (v) 5- to 6-membered heteroaryl containing 1-3 ring heteroatoms independently selected from N, S, and O;
• wherein R20 is H or C1-C3 alkyl;
• and Ra and Rb are independently H, C1-C3 alkyl, phenyl, —(C1-C3 alkylene)-O—(C1-C3 alkyl), C3-C6 cycloalkyl, —(C1-C3 alkylene)-(C3-C6 cycloalkyl), S(O)2(C1-C3 alkyl), or 4- to 8-membered heterocycloalkyl having 1-3 ring heteroatom or heteroatom groups independently selected from N, O, S, and S(O)2, wherein said phenyl, —(C1-C3 alkylene)-0-(C1-C3 alkyl), C3-C6 cycloalkyl, —(C1-C3 alkylene)-(C3-C6 cycloalkyl), and 4- to 8-membered heterocycloalkyl are substituted with 0-3 R2d;
• wherein each R2d, when present, is independently halo, —OH, C1-C3 alkyl, C1-C3 hydroxyalkyl, or C1-C3 haloalkyl;
• R3, when present, is H;
• —CN;
• C1-C3 alkyl;
• C1-C3 alkylene-NRcRd;
• C1-C3 haloalkyl;
• C1-C3 hydroxyalkyl;
• C3-C6 cycloalkyl;
• —S(O)2(C1-C3 alkyl);
• —CORc;
• —COORc;
• —CONRcRd;
• or 5-membered heteroaryl containing 1-3 ring heteroatoms independently selected from N, O, and S, and the 5-membered heteroaryl is substituted with 0-3 substituents independently selected from halo, OH, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 hydroxyalkyl, —C(O)NRcRd, —NRcRd, —CORc, —COORc, —S(O)2(C1-C3 alkyl), —NRc—S(O)2(C1-C3 alkyl), and —S(O)2—NRcRd;
• wherein Rc and Rd are independently H or C1-C3 alkyl, or Rc and Rd together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally having 1 additional ring heteroatom selected from N, S, and O, and the 5- or 6-membered heterocycloalkyl ring is substituted with 0-3 C1-C3 alkyl;
• X1 is CR4 or N;
• X2 is CR5 or N;
• R4, when present, is H;
• —CN;
• halogen;
• C1-C3 alkyl;
• C1-C3 haloalkyl;
• C1-C3 hydroxyalkyl;
• C2-C3 alkenyl;
• C3-C4 cycloalkyl;
• —S(O)2(C1-C3 alkyl);
• —C(O)OH;
• or 5- or 6-membered heteroaryl having 1 to 4 ring heteroatoms independently selected from N, S, and O, and the heteroaryl is substituted with 0-3 C1-C3 alkyl;
• R5 is H or C1-C3 alkyl;
• ring B is phenylene, or 5- to 6-membered heteroarylene having 1-3 ring heteroatoms independently selected from N, S, and O;
• J is —(CRgRh)n—Y1— or —Y1—(CRgRh)n—;
• wherein n is 1 or 2;
• Y1 is absent, CH2, CHF, CF2, O, S, S(O), or S(O)2;
• and each Rg and each Rh is independently H, halo, —OH, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C3-C4 cycloalkyl;
• or Rg and Rh together with the carbon atom to which they are attached form a 3- to 4-membered heterocycle ring having 1 ring heteroatom selected from N, O, and S, a C3-C4 cycloalkyl ring, or a C6-C8 spirocyclic ring, where each cycloalkyl ring or spirocyclic ring is substituted with 0-3 R3;
• and each R3 is independently selected from —CN, —OH, halogen, C1-C3 alkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy;
• and
• ring C is 5- to 6-membered heteroaryl containing 1-3 ring heteroatoms independently selected from N, S, and O, and the 5- to 6-membered heteroaryl is substituted with 0-3 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, and C3-C4 cycloalkyl.