Glp-1r modulating compounds

A method of treating GLP-1R mediated disease or condition comprising administering to a subject in need thereof a pharmaceutically effective amount of a compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is
• (a) a 5-membered heterorayl, optionally substituted with one to four R4, or
• (b) a 5-membered heteroaryl, wherein the heteroaryl is fused to a 5 or 6-membered ring having zero to three heteroatoms, each independelty N, O, or S, to form a fused ring system, wherein the fused ring system is optionally substituted with one to four R4;
• ring A is
• optionally substituted with one to three RA groups, each independently C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, halogen, —OH, —Cn, or N(R10a)(R10b);
• ring B is
• each of which is optionally substituted with one to three RB groups, each independently C1-6 alkyl or halogen;
• V is —C(R2a)(C2b);
• R2 is H, C1-6 alkyl, C1-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, C1-6 alkyl-C3-10 cycloalkyl, C1-6 alkyl-heterocyclyl, or C1-6 alkyl-heterorayl,
• wherein the alkyl, alkynyl, cycloalkyl, heterocyclyl or heteroaryl is each optionally substituted with one to four Z1, wherein each Z1 is independently C1-6 alkyl, C1-6 alkoxy, C1-6 hydorxyalkyl, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —OH, —Cn, C1-6 alkyl-CN, —O—C3-6 cycloalkyl or heteroaryl optionally substituted with 1 to 4 groups each independently C1-6 alkyl, C1-6 alkoxy, halogen, C1-6 haloalkyl, or C1-6 haloalkoxy;
• R3 is —C(O)OR3a;
• R3a is H, C1-6 alkyl-N(R9a(R9b), —C1-44 alkyl-N(R9a)C(O)-13 O-13 C1-4 alkyl-PP(O)OR9c)2, C1-4 alkyl-C(O)N(R9a)(R9b), —C1-4 alkyl-O—C(O)—C1-4 alkyl, —C1-4 alkyl-O—C(O)—O-13 C1-4alkyl, —C1-4 alkyl-O—C(O)—C1-4 alkyl-N(R9a(R9b), —C1-4 alkyl-O—C(O)—C1-4 alkyl-OP(O)(OR9c)2, —CH2CH(N(R9a)2)C(O)OR9b, —P9O)(OR9c)2, —OP(O)(OR9c)2, —CH2P(O)(OR9c)2, —CH2OP(O)(OR9c)2, —OCH2P(O)(OR9c)2, C(O)OCH2P9O)(OR9c)2, —P(O)(R9c)(OR9d), —OP(O)(R9c)(OR9d), —CH2P9O)(R9c)(OR9d), —OCH2P(O)(R9c)(OR9d), —C(O)OCH2P(O)(R9c)(OR9d), —P(O)(N(R9c)2)2, —OP(O)(N(R9c)2)2, —CH2P(O)(N(R9c)2)2, —OCH2O(O)(N(R9c)2)2, —C(O)OCH2P9O)(N(R9c)2)2, —P9O)(N(R9c)2)(OR9d), —OP(O)(N(R9c)2)(OR9d),
• —CH2P(O)(N(R9c)2)(OR9d), —OCH2P(O)(N(R9c)2)(OR9d),
• —C(O)OCH2P(O)(N(R9c)2)(OR9d), —P(O)(R9c)(C(R9d)2), —OP(O)(R9c)(N(R9d)2),
• —CH2P(O)(R9c)N(R9d)2), —OCH2P(O)(R9c)(N(R9d)2), —C(O)OCH2P(O)(R9c)(N(R9d)2), or C1-6 alkyl-heterocyclyl,
• wherein the alkyl or heterocyclyl is each ioptinally substituted with one to four halogens;
• each R4 is independetnly C1-9 alkyl, C1-8 haloalkyl, C1-6 alkoxy, C1-6 haloalkocy, C2-6 alkoxyalkyl, C2-6 alkenyl, C2-6 alkynyl, halgen, C3-15 cycloalkyl, heterocyclyl, C6-10 aryl, heteroaryl, oxo, —NO2, —N2, —CN, —O—R10a, —C(O)—R10a, —C(O)O—R10a,
• —C(O)—N(R10a)(R10b), —n(R10a)(R10b), —N(R10a)2(R10b)+, —N(R R10a)C(O)—R10b, —N(R10a)C(O))—R10b, —N(R10a)C(O)N9R10b(R10c), —N(R10a)S(O)2(R10b), —N R10aS(O)2N9R10b)(R10c), —N R10aS(O)2O(R10b), —OC(O)R10a, —OC(O)O R10a, —OC(O)—N(R10a(R10b), —S—R10a, —S(O) R10b, —S(O)(NJ) R10a, —S(OR)2R10a,
• —S(O)2N(R10a)(R10b), —S(O)(R R10b), R10b, or —Si(R10a),,
• wherein each alky, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one to four R5;
• Each R5 is independently C1-9 alkyl,C1-8 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C2-6 alkoxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-15 cycloalkyl, halogen C3-15 cycloalkkyl, heterocyclyl, C6-10 aryl, heteroaryl, oxo, —NO2, —N3, —CN, —O—R10a , —C(O)—R10a, —C(O)O—R10a, —C(O)—N(R10a)(R R10b), —N(R10a)(R10b),
• —N(R10a)C(O)—R10b, —N(R10c)C9O)O—R10b, —N(R10a)C(O)N(R10b)(R10c), —N(R10a)S(O)2(R10b), —N R10aS(O)2N9R10b(R10c), —N R10cS(O)2O(R10a) —S(O)(NJ)R10a, —S9O)2R10a, —S(O)2R(R10a)(R10b), —S(O)(N R10a)R10b, or —Si(R10a)2,
• wherein each alkyl, haloalkyl, alkenyl, alkynyl, cycoalkyl, hetocycyclyl, aryl, or heteroaryl is optionally substitued with one tor four R6;
• each R6 is independently C1-9 alkyl, C1-8 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, halogen, C3-15 cycloalkyl, heterocyclyl, C6-10 aryl, heteroaryl, oxo, —OH, —Cn, —NO2, —NH2, —N3, —SH, —O(C1-9 alkyl), —O(C1-8 haloalkyl), —O(C2-6 alkenyl, —O(C2-6 alkynyl), —O(C3-15 cycloalkyl),—I(heterocyclyl, —O(C6-10 aryl), —O)heteroaryl), —NH(C1-9 alkyly), —N(C1-8 haloalkyl), —NH(C2-6 alkenyl), —NH(C2-6 alkynyl), —NH(C3-15 cycloalkyl), —NH(heterocyclyl), —NH(C6-10 aryl), —NJ(heteroaryl), —N(C1-6 alkyl)2, —N(C1-8 haloalkyl), —NJ(C2-6 alkencyl), —NH(C2-6 alkynyl), —NH((C3-15 cycloalkyl), —N(heterocylcyl), —NH(C6-10 aryl), —NJ(heteroaryl), —N(C1-6 alkyl)2, —N(C1-8 haloalkyl)2, —N(C2-6 alkenyl)2, —N(C2-6 alkynyl)2, —N(C3-15 cycloalkyl)2, —N(heterocyclyl)2, —N(C6-10 aryl)2, —N(heteroaryl)2, —N(C1-9 alkyl)(C1-8 haloalkyl), —N(C1-9 alkyl)(C2-6 alkenyl), —N(C1-9 alkyl)(C2-6 alkynyl), —N(C1-9 alkyl)(C3-15 cycloalkyl), —N(C1-9 alkyl)(heterocyclyl), —N(C1-9 alkyl)(C6-10 aryl), —N(C1-9 alkyl)(heteroarylo), —C(O)(C1-9 alkyl), —C(O)(C1-8 haloalkyl), —C(O)(C2-6 alkenyl), —C(O)(C2-6 alkynyl), —C(O)(C3-15 cycloalkyl), —C(O)(heterocyclyl),
• —C(O)(C6-10 aryl), —C(O)(heteroaryl), —C(O)O(C1-9 alkyl), —C(I)O(C1-8 haloalkyl), —C(O)O(C2-6 alkeny;l), —C(O)O(C2-6 alkynyl), —C(O)(C3-15 cycloalkyl), —C(O)O(heterocyclyl), —C(O)O(C6-10 aryl), —C(O)O(heteroaryl),
• —C(O)NH2, —C(O)NJ(C1-10 alkyl), —C(O)NH(C1-8 haloalkyl), —C(O)NH(C2-6 alkenyl), —C(O)NH(C2-6 alkynyl), —C(O)N(C3-15 cycloalkyl),
• —C(O)NJ(heterocyclyl), —C(O)NC(C6-10 aryl), —C(O)NH(heteroaryl),
• —C(O)N(C1-9 alkyl)2, —C(O)N(C1-8 haloalkyl)2, —C(ON(C2-6 alkenyl)2,
• —C(O)N(C2-6 alkynyl)2, —C(O)N(C3-15 cycloalkyl)2,
• —C(ON(heterocyclyl)2, —C(O)N(R6-10 aryl)2, —C(O)N(heteroaryl)2,
• —NHC(O)(C1-9 alkyl), —NHC(O)(C1-8 haloalkyl), —NHC(O)(C2-6 alkenyl), —NHC(O)(C2-5 alkynyl), —NHC(O)(C3-15 cycloalkyl),
• —NHC(O)(heterocyclyl), —NHC(O)(C6-10 aryl), —NHC(O)(heteroaryl),
• —NHC(O)O(C1-9 alkyl), —NHC(O)O(C1-8 haloakll), —NHC(O)O(C2-6 alkenyl), —NHC(O)O(C2-6 alkynyl), —NHC9O0O(C3-15 cycloalkyl),
• —NHC(O)O(heterocyclyl), —NHG(O0O(C6-10 aryl), —NHC(O)O(heteroaryl),
• —NHC(O)NH(C1-9 alkyl), —NHC(o)NH(C1-8 haloaklyl), —NHC(O)NH(C2-6 alkenyl), —NHC(O)NH(C2-6 alkynyl), —NHC(O)NH(C3-15 cycloalkyl), —NHC(O)NH(heterocyclyl), —NHC(O)NH(C6-10 aryl),
• —NHC(O)NJ(heteroaryl), —NHS(O)(C1-9 alkyl), —N(C1-9 alkyl)(S(O)(C1-9 alkyl), —S(C1-9 alkyl), —(C1-8 haloaklyl), —S(C2-6 alkenyl), —S(C2-6 alkynyl),
• —S(C3-15 cycloalkyl), —S(heterocyclyl), —S(C6-10 aryl), —S(heteroaryl), —S(O)N(C1-9 alkyl)2, S(O)(C1-9 alkyl), —S(O)(C1-8 haloalkyl), —S(O)(C2-6 alkeyny;, —S(L)(C2-6 alkynyl), —S(O)(C3-15 cycloalkyl), —S(O)(Heterocylcl),
• —S(O)(C6-10 aryl), —S(O)(heteroaryl), —S(O)2(C1-9 alkyl), —S(O)2(C1-9 haloalkyl), —S(O)2(C2-6 alkenyl), —S(O)2(C2-6 alkynyl), —S(O)2(C3-15 cycloalkyl),
• —S(O)2(heterocyclyl, —SIO)2(C6-10 aryl), —S(O)2(heteroaryl), —Si(O)(NH)(C1-9 alkyl), —S(O)2NH(C1-9 alkyl), or —S(O)2N(C1-9 alkyl)2,
• wherein each alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optinally substituted with 1 to 3 C1-9 alkyl, C1-8 haloalkyl, halogen, —OH, —NH2, CO2H, —O(C-9 alkyl), —O)C1-8 haloalkyl), —O(C3-15 cycloalkyl), —o(heterocyclyl), —O(aryl), —O(heteroaryl), —NH(C1-9 alkyl), —NH(C107 haloalkyl), —NH(C3-15 cycloalkyl, —NH(heterocyclyl), —NK(aryl), —NH(heteroaryl), —N(C1-9 alkyl)2, —N(C3-15 cycloalkyl)2, —NHC(O)(C1-2 haloalkyl), —NKC(O)(C3-15 cycloalkyl), —NHC(O)(heterocyclel), —NKC(O)(aryl), —NKC(O)(heteroaryl), —NC(O))(C1-9 alkyl, —NHC(O)O(C1-8 haloalkyl), —NHC(o)O(C2-4 alkynyl, —NHC(O)O(C3-15 cycloalkyl), —NHC(O)O(heterocyclyl), —NHC(O)((aryl), —NHC(O)O(heteroaryl), —NHC(O)NC(C1-9 alkyl), S(O)2(C1-9 alkyl), —S(O)2(C1-8 haloalkyl), —S(O)2(C3-15 cycloalkyl), —S(O)2(heterocyclyl), —S(O)2(aryl), —S(O)2(heteroaryl), —SIO)(NH)(C1-9 alkyl, —S(O)2NH(C1-9 alkyl), or —S(O)2N(C1-9 alkyl)2,
• wherein the alkyl or heterocyclyl is each optionally substituted with one to four halogens;
• each R7a and R7b is independently —H, C1-6 alkyl, or halogen;
• each R9a and R9b is independently H, C1-6 alkyl, or C1-6 haloalkyl, or R9a and R9b together form a 6-membered heterocyclyl;
• each R9c, R9d, R10a, R10b, and R10c is independently H, C1-9 alkyl, C2-6 alkency;l, C2-6 alkynyl, C3-15 cycloalkyl, heterocyclyl, C6-10 aryl, or heteroaryl,
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is each optionally substitued with one to four R6;
• wherein each heterocyclyl has three tot welve ring members has one to four heteroatoms, each independently N, O, or S;
• and
• wherein each heteroaryl has five to twelce ring members and one to four heteroatoms, reach indeoendently N, O, or S.