PYRROLINONE CARBOXAMIDE COMPOUNDS USEFUL AS ENDOTHELIAL LIPASE INHIBITORS

摘要

The present invention provides compounds of Formula (I) or Formula (III): [INSERT CHEMICAL STRUCTURE HERE] (I) [INSERT CHEMICAL STRUCTURE HERE] (III) as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.;

主权项

1. A compound of Formula (I):or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
R1 is independently selected from the group consisting of: H, —((CH2)sO)r(C1-4 alkyl substituted with 0-1 Ra), C1-6 alkyl substituted with 0-3 Ra, C2-6 alkenyl substituted with 0-3 Ra, —SO2(phenyl), —(CH2)n(C3-6 cycloalkyl substituted with 0-3 Rc), —(CH2)n(CHRf)(CH2)m-phenyl, —(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; R2 is independently selected from the group consisting of: OR6, CN, and NR7R8; R3 is independently 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 independently selected from the group consisting of: H and C1-4 alkyl; R5 is independently selected from the group consisting of: C3-6 cycloalkyl, phenyl, naphthyl, 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 each moiety is substituted with 0-3 Rd; R6 is C1-6 alkyl substituted with 0-1 CO2H; R7 is independently 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 independently 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 independently a hydrocarbon or hydrocarbon-heteroatom linker optionally substituted with 0-2 Rg; wherein said hydrocarbon linker has one to eight carbon atoms and may be straight or branched, saturated or unsaturated; and said hydrocarbon-heteroatom linker may be saturated or unsaturated and has one to seven carbon atoms and one group selected from O, —CO—, S, —SO—, —SO2—, NH, and N(C1-4 alkyl); 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: halogen, OH, C1-6 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), CONH2, CONH(C1-4 alkyl), CON(C1-4 alkyl)2, NHCO2(C1-4 alkyl), NHSO2(C1-4 alkyl), SO2(C1-4 alkyl), and SO2NH2; 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; p, at each occurrence, is selected from 0, 1, and 2; and s and r are, independently at each occurrence, selected from 1, 2, 3, and 4.