Heterocyclic GLP-1 agonists

A compound of Formula (I):

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• Ring A is C6-10 aryl, C5-10 cycloalkyl, 5-10 membered heterocyclyl, or 5-10 membered heteroaryl, each of which is optionally substituted with from 1-5 substituents each independently selected from the group consisting of:
• halo, C1-6 alkyl, C1-6 haloalkyl, and C1-6 alkoxy;
• R1, R2 and R3 are each independently selected from the group consisting of H and C1-6 alkyl which is optionally substituted with from 1-6 substituents each independently selected from the group consisting of halo, —OH, and C1-6 alkoxy;
• L1 is selected from the group consisting of:
• —C(═O)—, —CH2—, —CH(C1-6 alkyl)-, and —S(═O)2;
• Ring B is selected from the group consisting of:
• wherein bb represents point of attachment to L1;
• R4, R5, R6, and R7 are independently selected from the group consisting of:
• H, halo, and C1-6 alkyl;
• L3 is a bond or C1-3 alkylene;
• L4 is a bond or C1-5 alkylene;
• R8a and R8b are independently selected from the group consisting of:
• H and C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of:
• halo and C3-15 cycloalkyl;
• or
• R8a and R8b taken together with the carbon atom to which each is attached forms a C3-15 cycloalkyl ring which is optionally substituted with from 1-3 independently selected C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with from 1-6 independently selected Rf,
• R9 is selected from the group consisting of:
• C(═O)OH, C(═O)(OC1-6 alkyl), C(═O)NR9aR9b, (IX-1), (IX-2), (IX-3), and (IX-4):
• R9a is H or C1-6 alkyl;
• R9b is H, C1-6 alkyl, C(═O)(C1-6 alkyl), S(O)0-2(C1-6 alkyl), or cyano;
• R9c, R9d, R9e, R9f, and R9g are each independently selected from the group consisting of:
• H;
• C1-6 alkyl optionally substituted with from 1-6 independently selected halo and C1-6 alkoxy;
• and C(═O)(C1-6 alkyl);
• Ring C is selected from the group consisting of 3-12 membered heterocyclyl;
• C3-10 cycloalkyl;
• and 5-10 membered heteroaryl, each of which is optionally substituted with from 1-3 RCa;
• each RCa is independently selected from the group consisting of:
• halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and NRcRd;
• or a pair of RCa on the same or different ring atoms, taken together with the ring atom(s) to which each is attached, forms a carbocyclic ring including from 3-8 ring atoms;
• L2 is selected from the group consisting of:
• wherein aa represents the point of attachment to Q;
• n1 is an integer from 1-3;
• L2A is a bond or C1-10 alkylene;
• RLa is selected from the group consisting of H, C1-6 alkyl, and C(═O)(C1-6 alkyl);
• each of RLb and RLc is independently selected from the group consisting of:
• H and C1-6 alkyl;
• Q is selected from the group consisting of:
• C1-10 alkyl;
• C3-15 cycloalkyl;
• 3-12 membered heterocyclyl;
• 5-10 membered heteroaryl;
• and C6-10 aryl, each of which is optionally substituted with from 1-6 independently selected RQ;
• each RQ is independently selected from the group consisting of:
• (a) halo;
• (b) cyano;
• (c) OH or oxo;
• (d) —NRcRd,
• (e) —C(═O)NRcRd or —S(O)2NRcRd,
• (f) —S(═O)0-2Re;
• (g) C1-6 alkyl optionally substituted with from 1-6 independently selected Rf,
• (h) C1-6 alkoxy optionally substituted with from 1-6 independently selected Rf;
• (i) 3-12 membered heterocyclyl optionally substituted with from 1-6 independently selected Rg;
• (j) C6-10 aryl optionally substituted with from 1-6 independently selected Rg;
• (k) 5-10 membered heteroaryl optionally substituted with from 1-6 independently selected Rg;
• (l) C3-8 cycloalkyl optionally substituted with from 1-6 independently selected Rg;
• (m) —P(═O)RaRb, and
• (n) —(CRhRh)q1—S(O)2-Le-Re, wherein q1 is 1, 2, or 3;
• Ra and Rb are independently selected from the group consisting of C1-6 alkyl which is optionally substituted with from 1-6 substituents each independently selected from the group consisting of C1-6 alkoxy, C3-6 cycloalkyl, and halo;
• C3-6 cycloalkyl optionally substituted with from 1-3 substituents each independently selected from the group consisting of C1-3 alkyl and halo;
• and C6-10 aryl optionally substituted with from 1-3 independently selected C1-3 alkyl;
• or
• Ra and Rb taken together with the phosphorous atom to which each is attached forms a ring including from 5-8 ring atoms, wherein from 0-2 ring atoms (in addition to the phosphorous attached to Ra and Rb) are heteroatoms each independently selected from the group consisting of:
• O, S, and N, wherein the ring is optionally substituted with from 1-3 independently selected C1-6 alkyl;
• each Rc and Rd are independently selected from the group consisting of:
• H, C1-6 alkyl, C3-6 cycloalkyl, C(═O)(C1-6 alkyl), C(═O)(C3-6 cycloalkyl), C(═O)O(C1-6 alkyl), S(O)1-2(C1-6 alkyl), and S(O)1-2(C3-6 cycloalkyl), wherein the C1-6 alkyl, C(═O)(C1-6 alkyl), C(═O)(C3-6 cycloalkyl), C(═O)O(C1-6 alkyl), S(O)1-2(C1-6 alkyl), and S(O)1-2(C3-6 cycloalkyl) are each optionally substituted with from 1-6 substituents independently selected from the group consisting of:
• —OH, halo, and C1-6 alkoxy;
• Re is H, or Re is selected from the group consisting of:
• C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, and 3-8 membered heterocyclyl, each of which is optionally substituted with from 1-3 substituents each independently selected from the group consisting of:
• halo, cyano, C1-3 alkyl, C1-3 haloalkyl, —OH, NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C1-3 alkoxy, and C1-3 haloalkoxy;
• Le is a bond, NRc, or O;
• each Rf is independently selected from the group consisting of halo, —OH, NRcRd, C1-6 alkoxy, C1-6 haloalkoxy, and 3-12 membered heterocyclyl which is optionally substituted with from 1-4 substituents each independently selected from the group consisting of —OH, C1-6 alkyl, and 3-12 membered heterocyclyl;
• each Rg is independently selected from the group consisting of:
• C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, NRcRd, cyano, halo, C3-6 cycloalkyl, and 3 to 12 membered heterocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6 alkyl and C(═O)C1-6 alkyl;
• and
• each occurrence of Rh is independently selected from the group consisting of:
• H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and halo;
• or
• a pair of Rh on the same or different carbon atom(s), taken together with the carbon atom(s) connecting them forms C3-6 cycloalkyl or 4-8 membered heterocyclyl, each of which is optionally substituted with from 1-3 substituents each independently selected from the group consisting of:
• halo, cyano, C1-3 alkyl, C1-3 haloalkyl, —OH, C1-3 alkoxy, and C1-3 haloalkoxy.