Inhibitors of MGAT2 dihydropyridinone for use in the treatment of metabolic disorders

摘要

A compound of formula (I): ** Formula ** or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, a solvate, or a hydrate thereof, in which: ring A is, independently, a 5-6 membered heteroaryl comprising carbon atoms and 1-4 heteroatoms selected from N, NRe, O and S; wherein said heteroaryl is substituted with 0-1 R6 and 0-2 R7; R1 is independently selected from: - (CH2) m- (C3-6 carbocycle substituted with 0-2 Rb and 0-2 Rg), - (CH2) m- (5- to 6-membered heteroaryl comprising carbon atoms and 1 -4 heteroatoms selected from N, NRe, O and S; where said heteroaryl is substituted with 0-1 Rb and 0-2 Rg) and (a C1-12 hydrocarbon chain substituted with 0-3 Ra; where said chain hydrocarbon can be linear or branched, saturated or unsaturated); R2 is independently selected from: C1-4 alkyl, C3-4 cycloalkyl and C1-4 haloalkyl; R3 is independently selected from: H, F, C1-4alkyl, and CN; R4 is independently selected from: H, F, and C1-4 alkyl; R3 and R4 can combine with the carbon atom to which they are attached to form a 3-6 membered carbocycle; R5 is independently selected from: H, halogen, C1-6 alkyl, CN, -NO2, Rc, -NH2, - (CH2) n- (X) t- (CH2) mRc, - CONH (C1-6 alkyl) and -NHCOX1SO2Ri; X is independently selected from the group consisting of O, S, NH, CONH, and NHCO; X1 is independently C1-4 hydrocarbon chain optionally substituted with C1-4 alkyl or C3-4 cycloalkyl; R6 is independently selected from: halogen, C1-2alkyl substituted with 0-2Rh, C1-4alkoxy, haloC1-4alkyl, haloalkoxyC1-4, CO (C1-4alkyl), - (CH2) m-C3 cycloalkyl -6, - (CH2) m-NRfRi, CN, ORi, SRi and (4-6 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NRe, O and S); R7 is independently selected from: halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl and C 1-4 haloalkoxy; alternatively, R6 and R7, together with the carbon atoms to which they are attached, combine to form a 5-6 membered carbocyclic ring or a 5-6 membered heterocyclic ring comprising carbon atoms and 1-3 selected heteroatoms between N, NRe, O and S; wherein said heterocycle is substituted with 0-2 Rg; Ra, in each case, is independently selected from: halogen, OH, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, N (C 1-4 alkyl) 2, COOH and - (CH2) n-Rc; Rb, in each case, is independently selected from: halogen, OH, C1-10 alkyl, C1-10 alkoxy, C1-10 haloalkyl, C1-10 haloalkoxy, C1-10 alkylthio, C1-10 haloalkylthio, N (C1- alkyl 4) 2, -CONH (C4-20alkyl), -CONH (haloC4-20alkyl), -O (CH2) sO (C1-6alkyl), -O (CH2) sO (haloC1-6alkyl), Rc and - (CH2) n- (O) t- (CH2) mRc; Rc, in each case, is independently selected from: C3-6 cycloalkyl substituted with 0-2 Rd, C3-6 cycloalkenyl substituted with 0-2 Rd, - (CH2) m- (phenyl substituted with 0-3 Rd) and a 5-6 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NRe, O and S; wherein said heterocycle is substituted with 0-2 Rd; Rd, in each case, is independently selected from: halogen, OH, CN, -NO2, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, tetrazolyl, OBn and phenyl; Re, in each case, is independently selected from: H, C 1-8 alkyl, C 1-8 haloalkyl, - (CH2) n-C 3-6 carbocycle, CO (C 1-4 alkyl) and COBn; Rf, in each case, is independently selected from: H and C1-4alkyl; Rg, in each case, is independently selected from: halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl and C 1-4 haloalkoxy; Rh, in each case, is independently selected from: OH, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl and C 1-4 haloalkoxy; Ri, in each case, is independently selected from the group consisting of C1-4alkyl, C3-4cycloalkyl, and phenyl; n, in each case, is independently 0 or 1; m, in each case, is independently 0, 1, 2, 3 or 4; s, in each case, is independently 1, 2 or 3; and t, in each case, is independently 0 or 1;