Modulators of LXR
View Patent ↗Compounds of the invention, such as compounds of formula (I): where n, m, A, B, R 1 , R 2 , R 3 , R 4 and R 5 are defined herein, are useful as modulators of the activity of liver X receptors. Pharmaceutical compositions containing the compounds and methods of using the compounds are also disclosed.
1. A compound of formula (I):
wherein:
n is 1 to 4;
m is 1 to 4;
ring A is furyl or thienyl, each substituted with n R 4 groups;
ring B is phenyl, naphthyl, heterocyclyl, or heteroaryl, each substituted with m R 5 groups;
R 1 is hydrogen, aralkyl or heteroarylalkyl;
R 2 is hydrogen, cyano, —R 7 —N(R 8 ) 2 , —R 7 —N(R 8 )S(O) 2 R 10 or —R 7 —N(R 8 )C(NR 8 )N(R 8 ) 2 ;
R 3 is hydrogen, alkyl, alkenyl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl;
each R 4 is independently hydrogen, halo, alkyl or haloalkyl;
each R 5 is independently selected from the group consisting of hydrogen, halo, nitro, alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, —R 7 —CN, —R 7 —N(R 8 ) 2 , —R 7 —OR 8 , —R 7 —O—R 9 —C(O)OR 8 , —R 7 —C(O)R 11 , —R 7 —C(O)OR 8 , —R 7 —C(O)N(R 8 ) 2 , —R 7 —C(O)N(R 8 )OR 8 , —R 7 —C(O)N(R 8 )N(R 8 ) 2 , —R 7 —C(O)N(R 8 )—R 9 —C(O)OR 8 , —R 7 —C(S)N(R 8 ) 2 , —R 7 —N(R 8 )C(O)R 8 , —R 7 —N(R 8 )C(O)OR 10 , —R 7 —S(O) t R 8 (where t is 0 to 2) and —R 7 —S(O) 2 N(R 8 ) 2 ;
R 6 is —OR 7 —, —N(R 8 )—, a direct bond, a straight or branched alkylene chain, a straight or branched alkenylene chain or a straight or branched alkynylene chain;
each R 7 is independently selected from a direct bond, a straight or branched alkylene chain or a straight or branched alkenylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl;
each R 9 is independently selected from a straight or branched alkylene chain or a straight or branched alkenylene chain;
each R 10 is independently selected from alkyl, aryl, aralkyl or cycloalkylalkyl; and
R 11 is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl;
as a mixture of stereoisomers, a racemic mixture thereof of stereoisomers, or as a tautomer;
or as a pharmaceutically acceptable salt or prodrug thereof.
2. The compound of claim 1 having the following formula (III):
wherein:
Y is oxygen or sulfur;
n is 1 or 2;
m is 1 to 4;
R 1 is aralkyl;
R 2 is hydrogen, cyano, —R 7 —N(R 8 ) 2 , —R 7 —N(R 8 )S(O) 2 R 10 or —R 7 —N(R 8 )C(NR 8 )N(R 8 ) 2 ;
R 3 is hydrogen or haloalkyl;
each R 4 is independently hydrogen, halo, alkyl or haloalkyl;
each R 5 is independently selected from the group consisting of hydrogen, halo, nitro, alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, —R 7 —CN, —R 7 —N(R 8 ) 2 , —R 7 —OR 8 , —R 7 —O C(O)OR 8 , —R 7 —O—R 9 —C(O)OR 8 , —R 7 —O—R 9 —OR 8 , —R 7 —C(O)R 11 , —R 7 —C(O)OR 8 , —R 7 —C(O)N(R 8 ) 2 , —R 7 —C(O)N(R 8 )OR 8 , —R 7 —C(O)N(R 8 )N(R 8 ) 2 , —R 7 —C(O)N(R 8 )—R 9 —C(O)OR 8 , —R 7 —C(S)N(R 8 ) 2 , —R 7 —N(R 8 )C(O)OR 10 , —R 7 —S(O) t R 8 (where t is 0 to 2) and —R 7 —S(O) 2 N(R 8 ) 2 ;
R 6 is —N(R 8 )—, a direct bond, a straight or branched alkylene chain, a straight or branched alkenylene chain or a straight or branched alkynylene chain;
each R 7 is independently selected from a direct bond, a straight or branched alkylene chain or a straight or branched alkenylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl;
each R 9 is independently selected from a straight or branched alkylene chain or a straight or branched alkenylene chain;
each R 10 is independently selected from alkyl, aryl, aralkyl or cycloalkylalkyl; and
R 11 is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl;
as a mixture of stereoisomers, a racemic mixture thereof of stereoisomers, or as a tautomer;
or as a pharmaceutically acceptable salt or prodrug thereof.
3. The compound of claim 2 wherein:
Y is oxygen or sulfur;
n is 1 or 2;
m is 1 to 4;
R 1 is aralkyl optionally substituted with one or more substituents selected from the group consisting of alkyl and halo;
R 2 is hydrogen, cyano, —R 7 —N(R 8 ) 2 , —R 7 —N(R 8 )S(O) 2 R 10 or —R 7 —N(R 8 )C(NR 8 )N(R 8 ) 2 ;
R 3 is hydrogen or haloalkyl;
each R 4 is independently hydrogen, halo, alkyl or haloalkyl;
each R 5 is independently selected from the group consisting of hydrogen, halo, nitro, alkyl, haloalkyl, —R 7 —CN, —R 7 —N(R 8 ) 2 , 13 R 7 —OR 8 , —R 7 —OC(O)OR 8 , —R 7 —O—R 9 —C(O)OR 8 , —R 7 —O—R 9 —OR 8 , —R 7 —C(O)R 11 , —R 7 —C(O)OR 8 , —R 7 —N(R 8 )C(O)OR 10 , —R 7 —S(O) t R 8 (where t is 0 to 2) and —R 7 —S(O) 2 N(R 8 ) 2 ;
R 6 is —N(R 8 )—, a direct bond, a straight or branched alkylene chain, a straight or branched alkenylene chain or a straight or branched alkynylene chain;
each R 7 is independently selected from a direct bond or a straight or branched alkylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl;
each R 9 is a straight or branched alkylene chain;
each R 10 is independently selected from alkyl, aryl, aralkyl or cycloalkylalkyl; and
R 11 is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.
4. The compound of claim 3 wherein Y is sulfur.
5. The compound of claim 4 wherein:
n is 1;
m is 1 to 3;
R 1 is benzyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 2 is hydrogen, cyano, —R 7 —N(R 8 ) 2 , —R 7 —N(R 8 )S(O) 2 R 10 or —R 7 —N(R 8 )C(NR 8 )N(R 8 ) 2 ;
R 3 is haloalkyl;
R 4 is hydrogen;
each R 5 is independently selected from the group consisting of hydrogen, halo, nitro, alkyl, haloalkyl, —R 7 —CN, —R 7 —N(R 8 ) 2 , —R 7 —OR 8 , —R 7 —OC(O)OR 8 ,
—R 7 —O—R 9 —C(O)OR 8 , —R 7 —O—R 9 OR 8 , —R 7 —C(O)R 11 , —R 7 —C(O)OR 8 , —R 7 —N(R 8 )C(O)OR 10 , —R 7 —S(O) t R 8 (where t is 0 to 2) and —R 7 —S(O) 2 N(R 8 ) 2 ;
R 6 is a direct bond, a straight or branched alkylene chain, a straight or branched alkenylene chain or a straight or branched alkynylene chain;
each R 7 is independently selected from a direct bond or a straight or branched alkylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl or cycloalkylalkyl;
each R 9 is a straight or branched alkylene chain;
each R 10 is independently selected from alkyl, aralkyl or cycloalkylalkyl; and
R 11 is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.
6. The compound of claim 5 wherein:
n is 1;
m is 1 to 3;
R 1 is benzyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 2 is cyano;
R 4 is hydrogen;
each R 5 is independently selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, —R 7 —OR 8 and —R 7 —O—R 9 —OR 8 ;
R 6 is a direct bond, a straight or branched ethylene chain, a straight or branched ethenylene chain or a straight or branched ethynylene chain;
each R 7 is a direct bond;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl or cycloalkylalkyl; and
each R 9 is a straight or branched ethylene chain.
7. The compound of claim 6 selected from the group consisting of the following:
1-(2,4-Difluoro-benzyl)-2-oxo-6-(5-m-tolyl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dichloro-benzyl)-2-oxo-6-(5-m-tolyl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dimethyl-benzyl)-2-oxo-6-(5-m-tolyl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Chloro-4-ethoxy-phenyl)-thiophen-2-yl]-1-(2,4-dichloro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dichloro-benzyl)-6-[5-(4-methoxy-3-methyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dichloro-benzyl)-2-oxo-4-trifluoromethyl-6-[5-(2,4,5-trimethyl-phenyl)-thiophen-2-yl]-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dichloro-benzyl)-6-[5-(4-methoxy-2-methyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3,5-Bis-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2,4-dichloro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dichloro-benzyl)-2-oxo-6-(5-o-tolyl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dichloro-benzyl)-6-[5-(3,4-dimethoxy-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dichloro-benzyl)-6-[5-(3,5-dichloro-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3,5-Dichloro-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(5-o-tolyl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3,4-dimethoxy-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Chloro-4-ethoxy-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methoxy-3-methyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(2-Bromo-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-4-trifluoromethyl-6-[5-(3-trifluoromethyl-phenyl)-thiophen-2-yl]-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(2-fluoro-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methoxy-3,5-dimethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-hydroxy-3,5-dimethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-hydroxymethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3,5-Bis-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Chloro-4-ethoxy-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3,4-dimethoxy-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methoxy-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-fluoro-4-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(5-phenylethynyl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(4-phenylethynyl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-[5-((E)-styryl)-thiophen-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-[4-((E)-styryl)-thiophen-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(5-phenethyl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-hydroxymethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-methoxy-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Chloro-4-methyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Chloro-4-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Chloro-4-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Chloro-4-methyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-methoxy-4-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethoxy-4-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-ethoxy-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-ethoxy-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethoxy-4-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-{5-[3-Chloro-4-(2,2,2-trifluoro-ethoxy)-phenyl]-thiophen-2-yl}-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-fluoro-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-fluoro-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Chloro-4-hydroxy-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-{5-[3-Chloro-4-(2-hydroxy-ethoxy)-phenyl]-thiophen-2-yl}-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethoxy-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethoxy-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-isopropoxy-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-isopropoxy-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethoxy-5-ethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethoxy-5-ethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethyl-5-isopropoxy-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethyl-5-isopropoxy-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile.
8. The compound of claim 5 wherein:
n is 1;
m is 1 or 2;
R 1 is benzyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 2 is hydrogen, cyano, —R 7 —N(R 8 ) 2 , —R 7 —N(R 8 )S(O) 2 R 10 or —R 7 —N(R 8 )C(NR 8 )N(R 8 ) 2 ;
R 3 is haloalkyl;
R 4 is hydrogen;
when m is 1, R 5 is hydrogen or —R 7 —S(O) t R 8 (where t is 0 to 2); or
when m is 2, one R 5 is —R 7 —S(O) t R 8 (where t is 0 to 2) or —R 7 —S(O) 2 N(R 8 ) 2 and the other R 5 is independently selected from the group consisting of alkyl, halo, haloalkyl and —R 7 —OR 8 ;
R 6 is a direct bond;
each R 7 is independently a direct bond or a straight or branched alkylene chain;
each R 8 is independently selected from hydrogen, alkyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl or cycloalkylalkyl; and
R 10 is alkyl, aryl, aralkyl or cycloalkylalkyl.
9. The compound of claim 8 selected from the group consisting of the following:
1-(2,4-Dichloro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Dimethyl-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-ethanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-3-dimethylaminomethyl-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-4-trifluoromethyl-1H-pyridin-2-one;
1-(2,4-Dichloro-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
N-{1-(2,4-Difluoro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridin-3-ylmethyl}-methanesulfonamide;
3-Diethylaminomethyl-1-(2,4-difluoro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-4-trifluoromethyl-1H-pyridin-2-one;
N-{1-(2,4-Difluoro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridin-3-ylmethyl}-guanidine;
1-(2,4-Difluoro-benzyl)-6-[4-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3,5-Bis-methanesulfonyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-methylsulfanyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-methylsulfanyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methyl-3-methylsulfanyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methanesulfinyl-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(5-methanesulfinyl-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-methanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-ethoxy-3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{5-[3-(propane-1-sulfinyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-{5-[3-(Butane-1-sulfinyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-[5-(3-phenylmethanesulfinyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Cyclopropylmethanesulfinyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethanesulfinyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{4-[3-(propane-1-sulfinyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-{4-[3-(Butane-1-sulfinyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-[4-(3-phenylmethanesulfinyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Cyclopropylmethanesulfinyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethanesulfinyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{4-[3-(propane-2-sulfinyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{5-[3-(propane-1-sulfonyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-{5-[3-(Butane-1-sulfonyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-[5-(3-phenylmethanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Cyclopropylmethanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{4-[3-(propane-1-sulfonyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-{4-[3-(Butane-1-sulfonyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Cyclopropylmethanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{4-[3-(propane-2-sulfonyl)-5-trifluoromethyl-phenyl]-thiophen-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-isopropyl-5-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-isopropyl-5-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Ethanesulfonyl-phenyl)-thiophen-2-yl]-1-(2-fluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Chloro-benzyl)-6-[5-(3-ethanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Fluoro-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Chloro-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Ethanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(2-fluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethyl-5-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethyl-5-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Chloro-benzyl)-6-[5-(3-ethanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-acetic acid;
1-(2-Chloro-benzyl)-6-[5-(3-isopropyl-5-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Fluoro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Chloro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethanesulfonyl-5-isopropyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethanesulfonyl-5-isopropyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Ethanesulfonyl-phenyl)-thiophen-2-yl]-1-(4-ethyl-2-fluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(4-Ethyl-2-fluoro-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(4-Ethyl-2-fluoro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Ethanesulfonyl-5-trifluoromethyl-phenyl)-thiophen-2-yl]-1-(4-ethyl-2-fluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(4-Ethyl-2-fluoro-benzyl)-6-[5-(3-isopropyl-5-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
4-(1,1-Difluoro-propyl)-1-(2-fluoro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
4-(1,1-Difluoro-propyl)-1-(2-fluoro-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
4-(1,1-Difluoro-propyl)-6-[5-(3-ethanesulfonyl-5-isopropyl-phenyl)-thiophen-2-yl]-1-(2-fluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-tert-Butyl-5-methanesulfonyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-tert-Butyl-5-methanesulfonyl-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethanesulfonyl-5-ethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-{5-[3-ethyl-5-(propane-1-sulfonyl)-phenyl]-thiophen-2-yl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-{5-[3-ethyl-5-(propane-2-sulfonyl)-phenyl]-thiophen-2-yl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethanesulfonyl-5-ethyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-{4-[3-ethyl-5-(propane-1-sulfonyl)-phenyl]-thiophen-2-yl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-{4-[3-ethyl-5-(propane-2-sulfonyl)-phenyl]-thiophen-2-yl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(4-Chloro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Ethanesulfonyl-5-isopropyl-phenyl)-thiophen-2-yl]-1-(2-fluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Chloro-benzyl)-6-[5-(3-ethanesulfonyl-5-isopropyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(4-Chloro-benzyl)-6-[5-(3-ethanesulfonyl-5-isopropyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-5-isopropyl-phenyl)-acetic acid;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-5-isopropyl-phenyl)-acetic acid;
1-(4-Chloro-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-4-(1,1-difluoro-heptyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-4-(1,1-difluoro-heptyl)-6-[5-(3-ethanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-4-(1,1-difluoro-heptyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-4-(1,1-difluoro-3-methyl-butyl)-6-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-4-(1,1-difluoro-3-methyl-butyl)-6-[5-(3-ethanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-4-(1,1-difluoro-3-methyl-butyl)-6-[5-(4-methanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile; and
4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-benzenesulfonamide.
10. The compound of claim 4 wherein:
n is 1;
m is 1 or 2;
R 1 is benzyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 2 is cyano;
R 3 is haloalkyl;
R 4 is hydrogen;
each R 5 is independently selected from the group consisting of halo, nitro, alkyl, —R 7 —CN, —R 7 —N(R 8 ) 2 , —R 7 —OR 8 , —R 7 —OC(O)OR 8 , —R 7 —O—R 9 —C(O)OR 8 , —R 7 —C(O)R 11 , —R 7 —C(O)OR 8 and —R 7 —N(R 8 )C(O)OR 10 ;
R 6 is —N(H)— or a direct bond;
each R 7 is independently a direct bond or a straight or branched alkylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl or cycloalkylalkyl;
each R 9 is a straight or branched alkylene chain;
R 10 is alkyl, aryl, aralkyl or cycloalkylalkyl; and
R 11 is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.
11. The compound of claim 10 selected from the group consisting of the following:
1-(2,4-Difluoro-benzyl)-6-[5-(3-formyl-4-methoxy-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
Carbonic acid tert-butyl ester 4-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl ester;
6-[5-(3-Chloro-4-cyano-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Cyano-4-ethoxy-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Cyano-4-ethoxy-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-ethoxy-3-nitro-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Amino-4-ethoxy-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
(2-Chloro-4-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenoxy)-acetic acid ethyl ester;
(2-Chloro-4-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenoxy)-acetic acid;
6-[5-(4-Amino-3-chloro-phenyl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-2-ethoxy-phenyl)-carbamic acid tert-butyl ester;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-2-ethoxy-phenyl)-carbamic acid tert-butyl ester;
4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-benzoic acid methyl ester;
3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-benzoic acid methyl ester;
3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-benzoic acid;
4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-benzoic acid;
3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-5-isopropyl-benzoic acid methyl ester;
3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-5-isopropyl-benzoic acid methyl ester;
3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N,N-dimethyl-thiobenzamide;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-acetic acid;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid;
(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-acetic acid;
(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid methyl ester;
(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-acetic acid methyl ester;
(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-5-isopropoxy-phenyl)-acetic acid;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-2-methoxy-phenyl)-acetic acid methyl ester;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-2-methoxy-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-5-isopropoxy-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-4-fluoro-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-4-methoxy-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-5-isopropoxy-phenyl)-acetic acid;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-2-methoxy-phenyl)-acetic acid;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-2-methoxy-phenyl)-acetic acid;
2-(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-2-methyl-propionic acid methyl ester;
2-(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-2-methyl-propionic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-4-fluoro-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-4-methoxy-phenyl)-acetic acid;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-4-(1,1-difluoro-heptyl)-6-oxo-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-acetic acid methyl ester;
(2-Chloro-4-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid methyl ester;
(2-Chloro-4-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid tert-butyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-4-(1,1-difluoro-3-methyl-butyl)-6-oxo-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-acetic acid methyl ester;
3-(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-propionic acid methyl ester;
3-(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-propionic acid methyl ester;
3-(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-phenyl)-propionic acid methyl ester; and
3-(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-propionic acid methyl ester.
12. The compound of claim 3 wherein Y is oxygen.
13. The compound of claim 12 wherein:
n is 1;
m is 1 to 3;
R 1 is benzyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 2 is cyano;
R 3 is haloalkyl;
R 4 is hydrogen;
each R 5 is independently selected from the group consisting of halo, nitro, alkyl, haloalkyl, —R 7 —CN, —R 7 —N(R 8 ) 2 , —R 7 —OR 8 , —R 7 —OC(O)OR 8 , —R 7 —O—R 9 —C(O)OR 8 , —R 7 —O—R 9 —OR 8 , —R 7 —C(O)R 11 , —R 7 —C(O)OR 8 , —R 7 —N(R 8 )C(O)OR 10 and —R 7 —S(O) t R 8 (where t is 0 to 2);
R 6 is a direct bond;
each R 7 is independently selected from a direct bond or a straight or branched alkylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl or cycloalkylalkyl;
each R 9 is a straight or branched alkylene chain;
R 10 is alkyl, aryl, aralkyl or cycloalkylalkyl; and
R 11 is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.
14. The compound of claim 13 wherein:
n is 1;
m is 1 to 3;
R 1 is benzyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 2 is cyano;
R 3 is trifluoromethyl;
R 4 is hydrogen;
each R 5 is independently selected from the group consisting of halo, alkyl, haloalkyl, —R 7 —OR 8 and —R 7 —O—R 9 —OR 8 ;
R 6 is a direct bond;
each R 7 is independently a direct bond or a straight or branched alkylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl or cycloalkylalkyl; and
each R 9 is a straight or branched ethylene chain.
15. The compound of claim 14 selected from the group consisting of the following:
6-[5-(3,5-Bis-trifluoromethyl-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(2-Chloro-5-trifluoromethyl-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3,4-dimethoxy-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-hydroxy-3-methoxy-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3,5-Bis-trifluoromethyl-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Chloro-4-ethoxy-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methoxy-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-fluoro-4-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-fluoro-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-methoxy-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Chloro-4-methyl-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Chloro-4-trifluoromethyl-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Chloro-4-trifluoromethyl-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-fluoro-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-fluoro-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(3-Chloro-4-methyl-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-ethoxy-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethoxy-4-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethoxy-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-isopropoxy-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethoxy-5-ethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethyl-5-isopropoxy-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile.
16. The compound of claim 12 wherein:
n is 1;
m is 1 or 2;
R 1 is benzyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 2 is hydrogen, cyano, —R 7 —N(R 8 ) 2 , —R 7 —N(R 8 )S(O) 2 R 10 or —R 7 —N(R 8 )C(NR 8 )N(R 8 ) 2 ;
R 3 is haloalkyl;
R 4 is hydrogen;
when m is 1, R 5 is hydrogen or —R 7 —S(O) t R 8 (where t is 0 to 2); or
when m is 2, one R 5 is —R 7 —S(O) t R 8 (where t is 0 to 2) and the other R 5 is independently selected from the group consisting of halo, haloalkyl and —R 7 —OR 8 ;
R 6 is a direct bond;
each R 7 is a direct bond;
each R 8 is independently selected from hydrogen, alkyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl or cycloalkylalkyl; and
R 10 is alkyl, aryl, aralkyl or cycloalkylalkyl.
17. The compound of claim 16 selected from the group consisting of the following:
1-(2,4-Difluoro-benzyl)-6-[5-(4-methanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methylsulfanyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-methanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-methylsulfanyl-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-methylsulfanyl-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methyl-3-methylsulfanyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-methanesulfonyl-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-methanesulfonyl-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethanesulfonyl-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{5-[3-(propane-2-sulfonyl)-5-trifluoromethyl-phenyl]-furan-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethanesulfonyl-5-trifluoromethyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{4-[3-(propane-1-sulfonyl)-5-trifluoromethyl-phenyl]-furan-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{4-[3-(propane-2-sulfonyl)-5-trifluoromethyl-phenyl]-furan-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-{5-[3-(propane-1-sulfonyl)-5-trifluoromethyl-phenyl]-furan-2-yl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-isopropyl-5-methanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethyl-5-methanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(3-ethyl-5-methanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(3-ethanesulfonyl-5-isopropyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Fluoro-benzyl)-6-[4-(4-methanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-4-(1,1-difluoro-propyl)-6-[4-(3-ethanesulfonyl-5-isopropyl-phenyl)-furan-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-tert-Butyl-5-methanesulfonyl-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Fluoro-benzyl)-6-[4-(3-methanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Ethanesulfonyl-phenyl)-furan-2-yl]-1-(2-fluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-{4-[3-ethyl-5-(propane-1-sulfonyl)-phenyl]-furan-2-yl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-{4-[3-ethyl-5-(propane-2-sulfonyl)-phenyl]-furan-2-yl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and
1-(2,4-Difluoro-benzyl)-6-[5-(3-methanesulfonyl-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile.
18. The compound of claim 13 wherein:
n is 1;
m is 1 or 2;
R 1 is benzyl optionally substituted with one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 2 is cyano;
R 3 is haloalkyl;
R 4 is hydrogen;
each R 5 is independently selected from the group consisting of halo, nitro, alkyl, —R 7 —CN, —R 7 —N(R 8 ) 2 , —R 7 —OR 8 , —R 7 —OC(O)OR 8 , —R 7 —O—R 9 —C(O)OR 8 , —R 7 —C(O)R 11 , —R 7 —C(O)OR 8 and —R 7 —N(R 8 )C(O)OR 10 ;
R 6 is a direct bond;
each R 7 is independently a direct bond or a straight or branched alkylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl or cycloalkylalkyl;
each R 9 is a straight or branched alkylene chain;
R 10 is alkyl, aryl, aralkyl or cycloalkylalkyl; and
R 11 is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.
19. The compound of claim 18 selected from the group consisting of the following:
6-[4-(3-Chloro-4-cyano-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(3-Cyano-4-ethoxy-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(4-ethoxy-3-nitro-phenyl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(4-Amino-3-chloro-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-2-ethoxy-phenyl)-carbamic acid tert-butyl ester;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-2-yl}-2-ethoxy-phenyl)-carbamic acid tert-butyl ester;
3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-5-isopropyl-benzoic acid methyl ester;
6-[4-(3-Amino-4-ethoxy-phenyl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-acetic acid;
(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-acetic acid;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-5-isopropyl-phenyl)-acetic acid;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-acetic acid methyl ester;
(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-acetic acid methyl ester;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-2-methoxy-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-5-isopropoxy-phenyl)-acetic acid;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-4-methoxy-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-4-fluoro-phenyl)-acetic acid methyl ester;
2-(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-2-methyl-propionic acid methyl ester;
(5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-2-methoxy-phenyl)-acetic acid;
(2-Chloro-4-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-acetic acid methyl ester;
(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-benzyl)-carbamic acid tert-butyl ester;
3-(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-propionic acid methyl ester; and
3-(4-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-phenyl)-propionic acid methyl ester.
20. A compound of having the following formula (V):
wherein:
n is 1 or 2;
m is 1 to 4;
Y is oxygen or sulfur;
R 1 is aralkyl;
R 2 is cyano or —R 7 —N(R 8 ) 2 ;
R 3 is haloalkyl;
each R 4 is independently hydrogen, halo, alkyl or haloalkyl;
is naphthyl, heterocyclyl or heteroaryl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, haloalkyl, heterocyclyl, —R 7 —OR 8 , —R 7 —CN, —R 7 —C(O)OR 8 , —R 7 —OC(O)R 10 and —R 7 —S(O) t R 8 (where t is 0 to 2);
R 6 is a direct bond;
each R 7 is independently selected from a direct bond, a straight or branched alkylene chain or a straight or branched alkenylene chain;
each R 8 is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl;
R 10 is alkyl, aryl, aralkyl or cycloalkylalkyl;
as a mixture of stereoisomers, a racemic mixture thereof of stereoisomers, or as a tautomer;
or as a pharmaceutically acceptable salt or prodrug thereof.
21. The compound of claim 20 wherein:
Y is —O—;
R 1 is benzyl optionally substituted by one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 3 is haloalkyl;
is a N-heteroraryl selected from the group consisting of pyrimidinyl and pyridinyl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, haloalkyl, morpholinyl, piperazinyl, —R 7 —CN, —R 7 —OR 8 , —R 7 —C(O)OR 8 ,
—R 7 —OC(O)R 10 and —R 7 —S(O) t R 8 (where t is 0 to 2);
each R 7 is independently a direct bond or a methylene chain;
each R 8 is hydrogen or alkyl; and
R 10 is alkyl or cycloalkylalkyl.
22. The compound of claim 21 selected from the group consisting of the following:
1-(2,4-Difluoro-benzyl)-6-[5-(6-methoxy-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(2,4-dimethoxy-pyrimidin-5-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(4-pyridin-4-yl-furan-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-5-trifluoromethyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-methylsulfanyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-methanesulfonyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-2-ethoxy-nicotinonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-isopropoxy-5-trifluoromethyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-methanesulfonyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-2-ethoxy-nicotinic acid ethyl ester;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-2-yl}-2-ethoxy-nicotinic acid ethyl ester;
1-(2,4-Difluoro-benzyl)-6-[4-(5-methyl-6-methylsulfanyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-furan-3-yl}-2-methanesulfonyl-nicotinic acid methyl ester;
1-(2,4-Difluoro-benzyl)-6-[4-(5-isopropenyl-6-methylsulfanyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-5-isopropenyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(5-isopropenyl-6-methanesulfonyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-4-(1,1-difluoro-propyl)-6-[4-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-furan-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethylsulfanyl-5-methyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-5-isopropyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(5-isopropyl-6-methanesulfonyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethanesulfonyl-5-methyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[4-(2-Chloro-pyridin-4-yl)-furan-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Fluoro-benzyl)-6-[4-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and
1-(2,4-Difluoro-benzyl)-2-oxo-6-[4-(6-piperazin-1-yl-pyridin-3-yl)-furan-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile.
23. The compound of claim 20 wherein:
Y is —O—;
R 1 is benzyl optionally substituted by one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 3 is haloalkyl;
is heterocyclyl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, haloalkyl, —R 7 —CN, —R 7 —OR 8 , —R 7 —C(O)OR 8 , —R 7 —OC(O)R 10 and —R 7 —S(O) t R 8 (where t is 0 to 2);
each R 7 is independently a direct bond or a methylene chain;
each R 8 is hydrogen or alkyl; and
R 10 is alkyl or cycloalkylalkyl.
24. The compound of claim 23 selected from the group consisting of the following:
6-(5-Benzo[1,3]dioxol-5-yl-furan-2-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and
1-(2,4-Difluoro-benzyl)-6-[5-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-furan-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile.
25. The compound of claim 20 wherein:
Y is —S—;
R 1 is benzyl optionally substituted by one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 3 is haloalkyl;
is a N-heteroaryl selected from the group consisting of pyridinyl, indolyl and pyrimidinyl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, haloalkyl, morpholinyl, piperazinyl, —R 7 —CN, —R 7 —OR 8 , —R 7 —C(O)OR 8 , —R 7 —C(O)OR 10 and —R 7 —S(O) t R 8 (where t is 0 to 2);
each R 7 is independently a direct bond or a methylene chain;
each R 8 is hydrogen or alkyl; and
R 10 is alkyl or cycloalkylalkyl.
26. The compound of claim 25 selected from the group consisting of the following:
1-(2,4-Difluoro-benzyl)-2-oxo-6-(5-pyridin-3-yl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(5-pyridin-4-yl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(4-pyridin-3-yl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(4-pyridin-4-yl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(1H-indol-5-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(5-pyridin-2-yl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-methoxy-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(2,4-dimethoxy-pyrimidin-5-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-(5-pyrimidin-5-yl-thiophen-2-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(2,6-Bis-trifluoromethyl-pyridin-4-yl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-ethoxy-5-trifluoromethyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-5-trifluoromethyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-methylsulfanyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-methanesulfonyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-methylsulfanyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-methanesulfonyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-2-ethoxy-nicotinonitrile;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-2-ethoxy-nicotinonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-ethoxy-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-isopropoxy-5-trifluoromethyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-[5-(1-oxy-pyridin-4-yl)-thiophen-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-2-ethoxy-nicotinic acid ethyl ester;
1-(2,4-Difluoro-benzyl)-6-[4-(5-methyl-6-methylsulfanyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(5-methyl-6-methylsulfanyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-2-methylsulfanyl-nicotinic acid methyl ester;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-2-methylsulfanyl-nicotinic acid methyl ester;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-2-methanesulfonyl-nicotinic acid methyl ester;
5-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-2-methanesulfonyl-nicotinic acid methyl ester;
1-(2,4-Difluoro-benzyl)-6-[5-(5-isopropenyl-6-methylsulfanyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(5-isopropenyl-6-methanesulfonyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Fluoro-benzyl)-6-[5-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-ethoxy-5-isopropenyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(4-Ethyl-2-fluoro-benzyl)-6-[5-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2-Chloro-benzyl)-6-[5-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-5-isopropenyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-ethoxy-5-isopropyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-ethylsulfanyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethoxy-5-isopropyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(5-isopropyl-6-methanesulfonyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-ethanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-ethoxy-2-methanesulfonyl-pyrimidin-4-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
4-(1,1-Difluoro-propyl)-1-(2-fluoro-benzyl)-6-[5-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[4-(6-ethylsulfanyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(2-methanesulfonyl-6-trifluoromethyl-pyridin-4-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
Acetic acid 1-(5-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-2-yl}-2-methanesulfonyl-pyridin-3-yl)-ethyl ester;
1-(2,4-Difluoro-benzyl)-6-[5-(2-ethanesulfonyl-6-ethyl-pyridin-4-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(4-Chloro-benzyl)-6-[5-(6-methanesulfonyl-5-methyl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-{5-[5-(1-hydroxy-ethyl)-6-methanesulfonyl-pyridin-3-yl]-thiophen-2-yl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(6-morpholin-4-yl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-[5-(2-Chloro-pyridin-4-yl)-thiophen-2-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(4-Chloro-benzyl)-6-[5-(3-ethanesulfonyl-phenyl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-[5-(6-piperazin-1-yl-pyridin-3-yl)-thiophen-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-2-oxo-6-[4-(6-piperazin-1-yl-pyridin-3-yl)-thiophen-2-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and
1-(2,4-Difluoro-benzyl)-6-[4-(6-morpholin-4-yl-pyridin-3-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile.
27. The compound of claim 20 wherein:
Y is —S—;
R 1 is benzyl optionally substituted by one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 3 is haloalkyl;
is heterocyclyl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, haloalkyl, —R 7 —CN, —R 7 —OR 8 , —R 7 —C(O)OR 8 , —R 7 —OC(O)R 10 and —R 7 —S(O) t R 8 (where t is 0 to 2);
each R 7 is independently a direct bond or a methylene chain;
each R 8 is hydrogen or alkyl; and
R 10 is alkyl or cycloalkylalkyl.
28. The compound of claim 27 selected from the group consisting of the following:
6-(4-Benzo[1,3]dioxol-5-yl-thiophen-2-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
6-(5-Benzo[1,3]dioxol-5-yl-thiophen-2-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-[5-(2,3-dihydro-benzofuran-5-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and
1-(2,4-Difluoro-benzyl)-6-[4-(2,3-dihydro-benzofuran-5-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile.
29. The compound of claim 20 wherein:
Y is —S—;
R 1 is benzyl optionally substituted by one or more substituents selected from the group consisting of chloro, bromo, fluoro, methyl or ethyl;
R 3 is haloalkyl;
is naphthyl; and
each R 5 is independently selected from hydrogen, alkyl, halo or haloalkyl.
30. The compound of claim 29 selected from the group consisting of the following:
1-(2,4-Dichloro-benzyl)-6-[5-(4-methyl-naphthalen-1-yl)-thiophen-2-yl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;
1-(2,4-Difluoro-benzyl)-6-(5-naphthalen-2-yl-thiophen-2-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and
1-(2,4-Difluoro-benzyl)-6-(5-naphthalen-1-yl-thiophen-2-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile.
31. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 .