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US 2014/0235673 A1Published application
Pyridinedione carboxamide inhibitors of endothelial lipase
AssigneeBristol-Myers Squibb Company
InventorsZulan Pi, John Llyod, Jennifer X. Qiao, Tammy C. Wang, George O. Tora
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of Formula (I) 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.
Claims13
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, 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 independently 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 independently 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 independently 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 independently selected from the group consisting of:
- OR6, CN, and NR7R8;
- R6 is independently selected from the group consisting of:
- H and 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 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:
- ═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), and Si(C1-4 alkyl)3;
- 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 is, independently at each occurrence, selected from 0, 1, and 2;
- n is, independently at each occurrence, selected from 0, 1, 2, 3, and 4;
- and
- p is, independently at each occurrence, selected from 0, 1, and 2;
- provided that:
- (i) when R1 is methyl, R2 and R3 are H, R5 is OH, and L is —(CH2)3—, then R4 is other than unsubstituted phenyl;
- (ii) when L is CH2, then R4 is other than halogen mono-substituted phenyl or methoxy bi-substituted phenyl;
- or
- (iii) when R1 is methyl, R2 and R3 are H, R5 is OH, and L is —(CH2)2—, then R4 is other than methoxy mono-substituted indolyl.
51 more elements
Dependencies are inferred from the claim text.