Inhibitors of diacylglycerol o-acyltransferase type 1 enzyme

A compound having formula (I), or a pharmaceutically acceptable salt, prodrug, salt of a prodrug, or a combination thereof

• wherein
• Q is phenyl or a monocyclic heteroaryl, optionally substituted with 1, 2 or 3 substituents as represented by T, wherein each T is independently alkyl, alkenyl, alkynyl, halogen, —CN, —NO2, —OR1, —OC(O)(R2), —N(Rw)(R1), —N(Rw)C(O)(R1), —N(Rw)—C(O)O(R1), —N(Rw)—C(O)N(R1)2, —N(Rw)—S(O)2(R2), —C(O)O(R1), —C(O)N(Rw)(R1), —C(O)R1, —SR1, —S(O)R2, —S(O)2R2, —S(O)2N(Rw)(R1), —(CRgRh)t—CN, —(CRgRh)t—NO2, —(CRgRh)t—OR1, —(CRgRh)t—OC(O)(R2), —(CRgRh)t—N(Rw)(R1), —(CRgRh)t—N(Rw)C(O)(R1), —(CRgRh)t—N(Rw)—C(O)O(R1), —(CRgRh)t—N(Rw)—C(O)N(R1)2, —(CRgRh)t—N(Rw)—S(O)2(R2), —(CRgRh)t—C(O)O(R1), —(CRgRh)t—C(O)N(Rw)(R1), —(CRgRh)t—C(O)R1, —(CRgRh)t—SR1, —(CRgRh)t—S(O)R2, —(CRgRh)t—S(O)2R2, —(CRgRh)t—S(O)2N(Rw)(R1) or haloalkyl;
• alternatively, two of the adjacent T substituents, together with the carbon atoms to which they are attached, form a monocyclic ring selected from the group consisting of phenyl, heterocycle and heteroaryl, wherein each ring is optionally further substituted with 1, 2 or 3 substituents selected from the group consisting of oxo, alkyl, alkenyl, alkynyl, halogen, —CN, —NO2, —OR1, —OC(O)(R2), —N(Rw)(R1), —N(Rw)C(O)(R1), —N(Rw)—C(O)O(R1), —N(Rw)—C(O)N(R1)2, —N(Rw)—S(O)2(R2), —C(O)O(R1), —C(O)N(Rw)(R1), —C(O)R1, —SR1, —S(O)R2, —S(O)2R2, —S(O)2N(Rw)(R1), —(CRgRh)t—CN, —(CRgRh)t—NO2, —(CRgRh)t—OR1, —(CRgRh)t—OC(O)(R2), —(CRgRh)t—N(Rw)(R1), —(CRgRh)t—N(Rw)C(O)(R1), —(CRgRh)t—N(Rw)—C(O)O(R1), —(CRgRh)t—N(Rw)—C(O)N(R1)2, —(CRgRh)t—N(Rw)—S(O)2(R2), —(CRgRh)t—C(O)O(R1), —(CRgRh)t—C(O)N(Rw)(R1), —(CRgRh)t—C(O)R1, —(CRgRh)t—SR1, —(CRgRh)t—S(O)R2, —(CRgRh)t—S(O)2R2, —(CRgRh)t—S(O)2N(Rw)(R1), and haloalkyl:
• A is phenyl, or a 4-, 5-, 6- or 7-membered monocyclic ring selected from the group consisting of heteroaryl and heterocycle, wherein each A is independently further unsubstituted or substituted with 1, 2, 3, 4 or 5 substitutents represented by Ra, and Ra is selected from the group consisting of oxo, —N(Rw)C(O)H, alkyl, alkenyl, alkynyl, halogen, —NO2, —CN, haloalkyl, G1, —(CReRf)q-G1, —Y1—Y3, —Y1—(CReRf)q—Y3, —Y1—(CReRf)q—Y2—Y3, and —Y1—(CReRf)q—Y2—(CReRf)q—Y3;
• or
• A is formula (a)
• wherein
• Va is C(R4), Vb is N or C(R5) and Vc is N;
• or
• Va is N, Vb is C(R5), and Vc is N or C(R6);
• R4 is hydrogen, halogen, alkyl, haloalkyl, —CN, —ORb, —SRb, —S(O)Rc, —S(O)2Rc, —N(Rb)(Rd), or heterocycle,
• R5 is hydrogen, alkyl, halogen, haloalkyl, —CN, —ORb, —SRb, —S(O)Rc, —S(O)2Rc, aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle:
• R6 is hydrogen, alkyl, halogen, haloalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocyclic:
• or
• R4 and R5, together with the carbon atoms to which they are attached, form a phenyl ring which is further unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of alkyl, halogen, —CN, —ORb, —SRb, and haloalkyl;
• R7 is hydrogen, alkyl, halogen, —CN, or haloalkyl:
• G1 is cycloalkyl, cycloalkenyl, heterocycle, heteroaryl, or aryl;
• Y1 and Y2, at each occurrence, are each independently O, S, S(O), S(O)2, N(Rw), —C(O), —OC(O)—, —N(Rw)C(O)—, —N(Rw)S(O)2—, —N(Rw)C(O)N(Rw)—, —OC(O)N(Rw)—, —N(Rw)C(O)O—, —C(O)O—, —C(O)N(Rw)—, or —S(O)2N(Rw)—:
• wherein the right side of the —OC(O)—, —N(Rw)C(O)—, —N(Rw)S(O)2—, —N(Rw)C(O)N(Rw)—, —OC(O)N(Rw)—, —N(Rw)C(O)O—, —C(O)O—, —C(O)N(Rw)—, and —S(O)2N(Rw)— moieties are connected to —(CReRf)q— or Y3:
• Y3 at each occurrence is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocycle, heteroaryl, or aryl;
• r and s are independently 1 or 2;
• X is X1, —(CRkRm)u—X1, —(CRkRm)u—C(O)—X2, or —C(O)—X2,
• X1 at each occurrence is independently heterocycle, or heteroaryl;
• X2 at each occurrence is independently heteroaryl, heterocycle, —OR11, —N(Rw)(R3), —N(Rw)—(CRnRq)w—C(O)OR11, —N(Rw)—(CRnRq)w—OR11, or —N(Rw)—(CRnRq)w—S(O)2R12;
• R11, at each occurrence, is independently hydrogen, alkyl, haloalkyl, arylalkyl, or heteroarylalkyl;
• R12, at each occurrence, is alkyl, haloalkyl, arylalkyl, or heteroarylalkyl;
• wherein the cycloalkenyl, cycloalkyl, heterocycle, heteroaryl, aryl, the aryl moiety of the arylalkyl, and the heteroaryl moiety of the heteroarylalkyl as represented by G1, Y3, X1, X2, R4, R5, R6, R11 and R12, are each optionally further substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, oxo, ethylenedioxy, methylenedioxy, —CN, —NO2, —OR1, —OC(O)(R2), —N(Rw)(R1), —N(Rw)C(O)(R1), —N(Rw)—C(O)O(R1), —N(Rw)—S(O)2(R2), —C(O)O(R1), —C(O)N(Rw)(R1), —C(O)R1, —SR1, —S(O)R2, —S(O)2R2, —S(O)2N(Rw)(R1), haloalkyl, —(CRgRh)v—CN, —(CRgRh)v—NO2, —(CRgRh)v—OR1, —(CRgRh)v—OC(O)(R2), —(CRgRh)v—N(Rw)(R1), —(CRgRh)v—N(Rw)C(O)(R1), —(CRgRh)v—N(Rw)—C(O)O(R1), —(CRgRh)v—N(Rw)—S(O)2(R2), —(CRgRh)v—C(O)O(R1), —(CRgRh)v—C(O)N(Rw)(R1), —(CRgRh)v—C(O)R1, —(CRgRh)v—SR1, —(CRgRh)v—S(O)R2, —(CRgRh)v—S(O)2R2, —(CRgRh)v—S(O)2N(Rw)(R1), and haloalkyl;
• q, t, u, v and w, at each occurrence, are each independently 1, 2, 3, 4, 5, or 6:
• R3 is hydrogen, alkyl, haloalkyl, —OH, —S(O)2R1, —C(O)OR1, heterocycle or heteroaryl, wherein the heteroaryl is connected to the nitrogen atom through the ring carbon atom, and the heterocycle and heteroaryl are optionally further substituted with 1 or 2 substitutents selected from the group consisting of alkyl, halogen, haloalkyl, —C(O)OR1, —OR1, and —N(Rw)(R1);
• Rb, Rd, Rx, Ry, Rza, Rzb, Rw, Re, Rg, Rh, Rk, Rm, Rn, Rq and R1, at each occurrence, are independently hydrogen, alkyl, or haloalkyl;
• Re and R2, at each occurrence, are independently alkyl or haloalkyl;
• and
• Rf, at each occurrence, is independently hydrogen, alkyl, halogen, haloalkyl, —OH, —O(alkyl), or —O(haloalkyl).