Pyridinedione carboxamide inhibitors of endothelial lipase

A compound of Formula (I):

• or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from the group consisting of:
• H, C1-6 alkyl substituted with 0-3 Ra, C2-6 alkenyl substituted with 0-3 Ra, and —(CH2)n—W—(CH2)m, R1a;
• W is selected from the group consisting of:
• a bond, NH, O, S, N(C1-4 alkyl), CO, CONH, CON(C1-4 alkyl), NHCO, SO2, NHSO2, SO2NH, NHCO2, and CHRf;
• R1a is selected from the group consisting of:
• C3-10 carbocycle and a 5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NRe, O, and S(O)p;
• and wherein said carbocycle and heterocycle are substituted with 0-3 Rc;
• R2 and R3 are, independently at each occurrence, selected from the group consisting of:
• H, halogen, CF3, OCF3, C1-6 alkyl substituted with 0-3 Ra, C2-6 alkenyl substituted with 0-3 Ra, —CO2(C1-4 alkyl), —SO2(phenyl), —(CH2)n—(C3-6 cycloalkyl substituted with 0-3 Rc), —(CH2)n-(phenyl substituted with 0-3 Rb), —(CH2)n-(naphthyl substituted with 0-3 Rb), and —(CH2)n-(5- to 10 membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NRe, O, and S(O)p), wherein said heterocycle is substituted with 0-3 Rc;
• R4 is selected from the group consisting of:
• C3-10 carbocycle and a 5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NRe, O, and S(O)p;
• wherein said carbocycle and heterocycle are substituted with 0-3 Rd;
• R5 is selected from the group consisting of:
• OR6, CN, and NR7R8;
• R6 is selected from the group consisting of:
• H and C1-6 alkyl substituted with 0-1 CO2H;
• R7 is selected from the group consisting of:
• H, C1-6 alkyl substituted with 0-1 Ra, —(CH2)n-(phenyl substituted with 0-3 Rb), and —(CH2)n-(5- to 6-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NRe, O, and S(O)p);
• and wherein said heterocycle is substituted with 0-3 Rc;
• R8 is selected from the group consisting of:
• H and C1-6 alkyl;
• alternatively, NR7R8 is a 5- to 6-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NRe, O, and S(O)p;
• L is X1—Y—X2;
• X1, and X2 are, independently at each occurrence, selected from the group consisting of:
• a bond, a hydrocarbon linker and a hydrocarbon-heteroatom linker;
• wherein said hydrocarbon linker and hydrocarbon-heteroatom linker may be substituted with 0-2 Rg;
• said hydrocarbon linker has one to five carbon atoms and may be saturated or unsaturated;
• and said hydrocarbon-heteroatom linker may be saturated or unsaturated and has zero to four carbon atoms and one group selected from O, —CO—, S, —SO—, —SO2—, NH, and N(C1-4 alkyl);
• Y is selected from the group consisting of:
• C3-10 carbocycle and a 4- to 10 membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NRe, O, and S(O)p;
• wherein each said carbocycle and heterocycle may be optionally substituted with one, two or three substituents independently selected from:
• halogen, OH, C1-4 alkyl, C1-4 haloalkyl, and C1-4 alkyoxy;
• alternatively, R4-L- is
• Ra is, independently at each occurrence, selected from the group consisting of:
• halogen, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, CF3, OCF3, CN, NH2, NO2, NH(C1-4 alkyl), N(C1-4 alkyl)2, CO2H, CO2(C1-4 alkyl), NHCO(C1-4 alkyl substituted with 0-1 NH2), N(C1-4 alkyl)CO(C1-4 alkyl), NHCO2(C1-4 alkyl), CONHSO2(C1-4 alkyl), SO2(C1-4 alkyl), CONH2, CONH(C1-4 alkyl), NHSO2 (C1-4 alkyl), N(C1-4 alkyl)SO2(C1-4 alkyl), and phenoxy;
• Rb is, independently at each occurrence, selected from the group consisting of:
• halogen, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, CF3, OCF3, OCF2CHF2, OCH2CF3, CN, NH2, NO2, NH(C1-4 alkyl), N(C1-4 alkyl)2, CO2H, CO2(C1-4 alkyl), CONH2, CONH(C1-4 alkyl), CON(C1-4 alkyl)2, NHCO2 (C1-4 alkyl), NHSO2(C1-4 alkyl), N(C1-4 alkyl)SO2(C1-4 alkyl), SO2(C1-4 alkyl), SO2NH2, phenyl, benzyl, and phenoxy;
• Rc is, independently at each occurrence, selected from the group consisting of:
• ═O and Rb;
• Rd is, independently at each occurrence, selected from the group consisting of:
• ═O, halogen, OH, C1-6 alkyl substituted with 0-1 OH, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, CF3, OCF3, OCF2CF2H, OCH2CF3, CN, NH2, NO2, NH(C1-4 alkyl), N(C1-4 alkyl)2, CO2H, CO2(C1-4 alkyl), CO(C1-4 alkyl), NHCO(C1-4 alkyl), —CH2NHCO(C1-4 alkyl), CONH2, CONH(C1-4 alkyl), CON(C1-4 alkyl)2, SO2(C1-4 alkyl), SO2NH2, —SO2NH(C1-4 alkyl), —SO2NH(C3-6 cycloalkyl), —NHSO2(C1-4 alkyl), —CH2NHSO2(C1-4 alkyl), Si(C1-4 alkyl)3, and phenyl optionally substituted with one or two substituents independently selected from:
• halogen, OH, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkyoxy, and NHCO(C1-4 alkyl);
• Re is, independently at each occurrence, selected from the group consisting of:
• H, C1-4 alkyl, CO(C1-4 alkyl), CO2(C1-4 alkyl), CO2(benzyl), and —(CH2)n-(phenyl optionally substituted with 0-2 halogens);
• Rf is, independently at each occurrence, selected from the group consisting of:
• C1-4 alkyl, C2-4 alkenyl, CO2(C1-4 alkyl), CONH2, C3-6 cycloalkyl, phenyl, and benzyl;
• Rg is, independently at each occurrence, selected from the group consisting of:
• halogen, OH, C1-4 alkyl, C2-4 alkenyl, C1-4 haloalkyl, C1-4 alkyoxy, CO2(C1-4 alkyl), C3-6 cycloalkyl, and phenyl;
• m, at each occurrence, is selected from 0, 1, and 2;
• n, at each occurrence, is selected from 0, 1, 2, 3, and 4;
• and
• p, at each occurrence, is selected from 0, 1, and 2.