Inhibitors of diacylglycerol O-acyltransferase 1 (DGAT-1) and uses thereof

A compound of Formula (I), or a pharmaceutically acceptable salt or a stereoisomer thereof,

• Q-G1-G2-G3-G4-Z Formula (I)
• wherein Q is Q1;
• Q1 is
• wherein J is selected from —NRaRb or —ORa;
• X is selected from the group consisting of C(R4) and N;
• E is selected from the group consisting of O and S;
• R1 is H;
• Ra and Rb are independently selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, fluoro(C1-C8)alkyl, (C3-C8)cycloalkyl, aryl, heteroaryl and aryl(C1-C4)alkyl;
• R2 and R3 are (C1-C8)alkyl;
• and
• each R4 is independently selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, fluoro(C1-C8)alkyl, aryl, aryl(C1-C4)alkyl, C(O)Ra, CO2Ra and C(O)NRaRb;
• G1 is phenylene and G3 is cyclo(C3-C8)alkylene;
• G2 is a bond;
• wherein X is selected from null, O, NH, CO, CHOH, S or S(O)2;
• and Y is selected from (C1-C4)alkylene, C3-C8-cycloalkylene or heterocycloalkylene, —CH(R9)C(R10R11)— or —N(R9)C(R10R11)—;
• wherein:
• R10 and R11 are both hydrogen, and R9 is hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, phenoxy-(C2-C6)alkyl, 1-methyl-1H-indol-3-yl, bis[(C1-C6)alkyl]amino-(C2-C6)alkyl, 1-piperidinyl-(C2-C6)alkyl, 1-pyrrolidinyl-(C2-C6)alkyl, or 1-morpholinyl-(C2-C6)alkyl;
• or
• R10 and R11 are both hydrogen and R9 is R12(CH2)m, where m is 0 to 3, and R12 is phenyl optionally substituted with one or more halogen, hydroxy, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl or cyano;
• or
• R10 and R11 are both hydrogen and R9 is R12(CH2)m, where m is 0 to 3, and R12 is 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl, each of which is optionally substituted with halogen, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl or cyano;
• or
• R9 is hydrogen, and R10 and R11 together with the carbon atom to which they are attached, form a three to five-membered ring, with 0 to 2 heteroatoms independently selected from 0, S or N;
• or
• R10 is hydrogen, and R9 and R11 together with the two carbon atoms to which they are attached, form a three- to six-membered ring with 0 to 2 heteroatoms independently selected from O, S or N;
• Z is
• wherein, X1 and X2 are independently selected from null, (C(RaRb))n, O, NRa, S or CO and n is 0 or 1;
• W is selected from H, (C1-C6)alkyl, aryl, heteroaryl or (C3-C8)cycloalkyl;
• wherein each of the (C1-C6)alkyl, aryl, heteroaryl and cycloalkyl is independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, —CN, halogen, ethylenedioxy, methylenedioxy, haloalkyl, —ORa, —O—C(O)(Ra), —S(Ra), —S(O)(Rb), —S(O)2(Rb), —C(O)(Ra), —C(O)(ORa), —N(Ra)2, —N(Ra)—C(O)(Ra), —C(O)N(Ra)2, —S(O)2N(Ra)2, —(CRaRb)tORa, —(CRaRb)t—O—C(O)(Ra), —(CRaRb)tS(Ra), —(CRaRb)tS(O)(Rb), —(CRaRb)tS(O)2(Rb), —(CRaRa)tC(O)(Ra), —(CRaRb)tC(O)(ORa), —(CRaRb)tN(RaRb)—(CRaRb)tN(Ra)—C(O)(Ra), —(CRaRb)tC(O)N(Ra)2, —(CRaRa)tS(O)2N(Ra)2 and —(CRaRb)tRa, —(CRaRb)tP(O)(OH)2, and —(CRaRb)tP(O)(OH)(Ra), wherein t is an integer of 1, 2, 3, or 4 and Ra and Rb are independently selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, fluoro(C1-C8)alkyl, (C3-C8)cycloalkyl, aryl, heteroaryl and aryl(C1-C4)alkyl;
• and
• X1 and X2 may be combined to form a 5-, 6- or 7-membered ring having from 0 to 3 heteroatoms selected from the group consisting of NRa, O and S;
• or X1 or X2 may be combined with W to form a 5-, 6- or 7-membered fused ring having from 0 to 3 heteroatoms selected from the group consisting of NRa, O and S;
• with a proviso that when X2 is O and Q is Q1, then X1 is not (C(RaRb))n.