Modulators of LXR

• US 8,013,001 B2
• Filed: 12/17/2008
• Issued: 09/06/2011
• Est. Priority Date: 12/21/2001
• Status: Expired due to Fees

• Current Assignee: Exelixis Incorporated
• Original Assignee: Exelixis Incorporated
• Inventors: Wang, Haixia, Stevens, William C. Jr., Schweiger, Edwin J., Lu, Shao Po, Xie, Yinong, Johnson, Alan T., Bayne, Christopher D., Mohan, Raju, Nyman, Michael C.
• Primary Examiner(s): NOLAN, JASON MICHAEL
• Application Number:
  US12/337,591
• Publication Number:
  US 20100056582A1
• Time in Patent Office: 993 Days
• Field of Search: 546/286, 546/290, 546/301, 546/302, 514/345
• US Class Current: 514/345
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 213/84 Nitriles
• CPC Class Codes: C07D 213/85 in position 3
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links

Abstract

Compounds of the invention, such as compounds of formula (I):

• • where n, m, A, B, R¹, R², R³, R⁴ and R⁵ 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.

Claims

1. A compound having the following formula (II):

2. The compound of claim 1 wherein:

n is 0 or 1;

m is 0 to 2;

R¹ is aralkyl or heteroarylalkyl;

R² is cyano;

R³ is haloalkyl;

R⁴ is halo, alkyl or haloalkyl;

each R⁵ is independently selected from the group consisting of halo, nitro, alkyl, alkenyl, haloalkyl, heterocyclyl, heteroaryl, —

R⁷—

CN, —

R⁷—

N(R⁸)₂, —

R⁷—

OR⁸, —

R⁷—

O—

R⁹—

C(O)OR⁸, —

R⁷—

C(O)R¹¹, —

R⁷—

C(O)OR⁸, —

R⁷—

C(O)N(R⁸)₂, —

R⁷—

C(O)N(R⁸)OR⁸, —

R⁷—

C(O)N(R⁸)N(R⁸)₂, —

R⁷—

C(O)N(R⁸)—

R⁹—

C(O)OR⁸, —

R⁷—

C(S)N(R⁸)₂, —

R⁷—

N(R⁸)C(O)OR¹⁰, —

R⁷—

S(O)_tR⁸ (where t is 0 to

     2) and —

R⁷—

S(O)₂N(R⁸)₂;

R⁶ is —

OR⁷—

, a direct bond, a straight or branched alkenylene chain or a straight or branched alkynylene chain;

each R⁷ is independently selected from a direct bond or a straight or branched alkylene chain;

each R⁸ is independently selected from hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl;

each R⁹ is a straight or branched alkylene chain optionally substituted by aryl or heteroaryl;

R¹⁰ is alkyl, aryl, aralkyl or cycloalkylalkyl; and

R¹¹ is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.

3. The compound of claim 2 wherein R⁶ is —

OR⁷—

.

4. The compound of claim 3 wherein R¹ is aralkyl optionally substituted with one or more substituents independently selected from alkyl, halo or haloalkyl.

5. The compound of claim 4 wherein

n is 0 or 1;

m is 0 to 2;

R² is cyano;

R³ is trifluoromethyl;

R⁴ is methyl, 1-methylethyl or chloro;

each R⁵ is independently selected from the group consisting of halo, alkyl, alkenyl or haloalkyl.

6. The compound of claim 5 wherein each R⁵ is independently selected from chloro, bromo, fluoro, methyl, ethyl, 1-methylethyl, 1,1-dimethylethyl, ethenyl or trifluoromethyl.

7. The compound of claim 6 selected from the group consisting of the following:

1-(2,4-Dimethyl-benzyl)-6-[4-(3-isopropyl-phenoxy)-3-methyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(4-tert-Butyl-phenoxy)-3-methyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(4-fluoro-phenoxy)-3-methyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2,4-dimethyl-phenoxy)-3-methyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2,5-dimethyl-phenoxy)-3-methyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2,6-dimethyl-phenoxy)-3-methyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(2-Chloro-phenoxy)-3-methyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(3-Chloro-phenoxy)-3-methyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[3-methyl-4-(2-trifluoromethyl-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[3-methyl-4-(3-trifluoromethyl-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(3-Bromo-phenoxy)-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(4-Bromo-phenoxy)-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(3-Benzyloxy-phenoxy)-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2,4-dimethyl-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(3,5-Bis-trifluoromethyl-phenoxy)-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(4-Benzyloxy-phenyl)-1-(2,4-dichloro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dichloro-benzyl)-2-oxo-6-(4-phenoxy-phenyl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-(4-phenoxy-phenyl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2-Chloro-4-fluoro-benzyl)-2-oxo-6-(4-phenoxy-phenyl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(4-Benzyloxy-phenyl)-1-(2-chloro-4-fluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dichloro-benzyl)-2-oxo-4-pentafluoroethyl-6-(4-phenoxy-phenyl)-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-(3-isopropyl-4-phenoxy-phenyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-(3-isopropyl-4-o-tolyloxy-phenyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2-ethyl-phenoxy)-3-isopropyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2,5-dimethyl-phenoxy)-3-isopropyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2,4-dimethyl-phenoxy)-3-isopropyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(3,4-dimethyl-phenoxy)-3-isopropyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-(3-isopropyl-4-m-tolyloxy-phenyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[3-isopropyl-4-(3-isopropyl-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[3-isopropyl-4-(4-isopropyl-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-(3-isopropyl-4-p-tolyloxy-phenyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(4-tert-Butyl-phenoxy)-3-isopropyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[3-isopropyl-4-(4-vinyl-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(4-ethyl-2-methyl-phenoxy)-3-methyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(4-ethyl-2-methyl-phenoxy)-3-isopropyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2-ethyl-4-methyl-phenoxy)-3-methyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(2-ethyl-4-methyl-phenoxy)-3-isopropyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(4-Benzyloxy-3-chloro-phenyl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[3-Chloro-4-(4-fluoro-phenoxy)-phenyl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and

1-(2,4-Difluoro-benzyl)-6-[4-(4-fluoro-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile,

or a pharmaceutically acceptable salt of any of the foregoing.

8. The compound of claim 4 wherein:

n is 0 or 1;

m is 1 or 2;

R² is cyano;

R³ is trifluoromethyl;

R⁴ is methyl, 1-methylethyl or chloro;

each R⁵ is independently selected from the group consisting of haloalkyl, —

R⁷—

CN, —

R⁷—

N(R⁸)₂, —

R⁷—

OR⁸ and R⁷—

O—

R⁹—

C(O)OR⁸

each R⁷ is independently selected from a direct bond or methylene chain;

each R⁸ is independently selected from hydrogen, alkyl, aryl and aralkyl; and

R⁹ is a methylene chain.

9. The compound of claim 8 selected from the group consisting of the following:

6-[4-(4-Dimethylamino-phenoxy)-3-methyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(4-methoxy-phenoxy)-3-methyl-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(3-Cyano-phenoxy)-3-methyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(4-Benzyloxy-phenoxy)-3-methyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(3-Benzyloxy-phenoxy)-3-methyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(3-Cyano-phenoxy)-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(4-Cyano-phenoxy)-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(4-Dimethylamino-phenoxy)-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(4-hydroxy-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(3-hydroxy-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(4-hexyloxy-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-{4-[4-(3-methyl-butoxy)-phenoxy]-phenyl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(3-hexyloxy-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-{4-[3-(3-methyl-butoxy)-phenoxy]-phenyl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-phenoxy)-acetic acid benzyl ester;

(4-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-phenoxy)-acetic acid benzyl ester;

1-(2,4-Dimethyl-benzyl)-2-oxo-6-[4-(4-phenylamino-phenoxy)-phenyl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(4-Benzylamino-phenoxy)-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-[4-(3-hydroxymethyl-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(3-Benzyloxy-phenoxy)-3-isopropyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[4-(4-Benzyloxy-phenoxy)-3-isopropyl-phenyl]-1-(2,4-dimethyl-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-[4-(3-hydroxy-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-[4-(4-hydroxy-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and

6-[4-(3-Cyano-4-trifluoromethyl-phenoxy)-phenyl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile,

or a pharmaceutically acceptable salt of any of the foregoing.

10. The compound of claim 4 wherein:

n is 0 or 1;

m is 1 or 2;

R² is cyano;

R³ is trifluoromethyl;

R⁴ is methyl, 1-methylethyl or chloro;

each R⁵ is independently selected from the group consisting of heteroaryl, —

R⁷—

OR⁸, —

R⁷—

C(O)R¹¹, —

R⁷—

C(O)OR⁸, —

R⁷—

C(O)N(R⁸)₂, —

R⁷—

C(O)N(R⁸)OR⁸, —

R⁷—

C(O)N(R⁸)N(R⁸)₂, —

R⁷—

C(O)N(R⁸)—

R⁹—

C(O)OR⁸, —

R⁷—

C(S)N(R⁸)₂ and —

R⁷—

S(O)_tR⁸ (where t is 0 to

     2);

each R⁷ is independently selected from a direct bond or a straight or branched alkylene chain;

each R⁸ is independently selected from hydrogen, alkyl, haloalkyl, aryl, aralkyl, aralkenyl, cycloalkyl or heterocyclyl optionally substituted with hydroxy;

R⁹ is a straight or branched alkylene chain (optionally substituted by phenyl or imidazolyl); and

R¹¹ is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.

11. The compound of claim 10 wherein:

m is 1 or 2;

each R⁵ is independently selected from —

R⁷—

OR⁸, —

R⁷—

C(O)R¹¹, —

R⁷—

C(O)OR⁸, —

R⁷—

C(O)N(R⁸)₂, —

R⁷—

C(O)N(R⁸)OR⁸ or —

R⁷—

C(O)N(R⁸)N(R⁸)₂;

each R⁷ is independently selected from a direct bond or methylene;

each R⁸ is independently selected from hydrogen, methyl, ethyl, 1,1-dimethylethyl, benzyl, 2-phenylethyl, cyclohexyl or piperidinyl optionally substituted by hydroxy; and

R¹¹ is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.

12. The compound of claim 11 selected from the group consisting of the following:

4-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-2-methyl-phenoxy}-benzoic acid methyl ester;

3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-2-methyl-phenoxy}-benzoic acid methyl ester;

4-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoic acid;

3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N-methyl-benzamide;

3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N,N-dimethyl-benzamide;

1-(2,4-Dimethyl-benzyl)-2-oxo-6-{4-[3-(piperidine-1-carbonyl)-phenoxy]-phenyl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-{4-[3-(3-hydroxy-piperidine-1-carbonyl)-phenoxy]-phenyl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

N-Benzyl-3-{4-[5-cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzamide;

3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoic acid N′

-phenyl-hydrazide;

3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N-cyclopentyl-benzamide;

3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N-methoxy-N-methyl-benzamide;

3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N—

((S)-1-phenyl-ethyl)-benzamide;

3-{4-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N,N-dimethyl-benzamide;

3-Benzyloxy-5-{4-[5-cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoic acid methyl ester;

3-Benzyloxy-5-{4-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N,N-dimethyl-benzamide;

3-{4-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-5-hydroxy-N,N-dimethyl-benzamide;

2-Benzyloxy-5-{4-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N,N-dimethyl-benzamide;

5-{4-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-2-hydroxy-N,N-dimethyl-benzamide;

3-{4-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N-methyl-benzamide;

N-tert-Butyl-3-{4-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzamide; and

1-(2,4-Difluoro-benzyl)-2-oxo-6-{4-[3-(piperidine-1-carbonyl)-phenoxy]-phenyl}-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile,

or a pharmaceutically acceptable salt of any of the foregoing.

13. The compound of claim 4 wherein:

n is 0 or 1;

m is 1 or 2;

R² is cyano;

R³ is trifluoromethyl;

R⁴ is methyl, 1-methylethyl or chloro;

each R⁵ is independently selected from the group consisting of heteroaryl, —

R⁷—

C(O)N(R⁸)—

R⁹—

C(O)OR⁸, —

R⁷—

C(S)N(R⁸)₂ and —

R⁷—

S(O)_tR⁸ (where t is 0 to

     2);

each R⁷ is independently selected from a direct bond or a straight or branched alkylene chain;

each R⁸ is independently selected from hydrogen or alkyl, haloalkyl, aryl, aralkyl, aralkenyl, cycloalkyl or heterocyclyl; and

R⁹ is a straight or branched alkylene chain (optionally substituted by phenyl or imidazolyl).

14. The compound of claim 13 wherein:

n is 0 or 1;

m is 1;

R² is cyano;

R³ is trifluoromethyl;

R⁴ is chloro;

R⁵ is —

R⁷—

C(O)N(R⁸)—

R⁹—

C(O)OR⁸;

R⁷ is a direct bond;

each R⁸ is independently hydrogen or alkyl; and

R⁹ is a straight or branched alkylene chain optionally substituted by phenyl or imidazolyl.

15. The compound of claim 14 selected from the group consisting of the following:

(S)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-propionic acid methyl ester;

(R)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-propionic acid methyl ester;

(S)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-3-methyl-butyric acid methyl ester;

(R)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-3-methyl-butyric acid methyl ester;

(S)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-4-methyl-pentanoic acid methyl ester;

(R)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-4-methyl-pentanoic acid methyl ester;

(S)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-3-phenyl-propionic acid methyl ester;

(R)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-3-phenyl-propionic acid methyl ester;

(S)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester;

(R)-2-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester;

(S)-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-phenyl-acetic acid methyl ester; and

(R)-(3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-benzoylamino)-phenyl-acetic acid methyl ester,

or a pharmaceutically acceptable salt of any of the foregoing.

16. The compound of claim 13 wherein:

n is 0 or 1;

m is 1;

R² is cyano;

R³ is trifluoromethyl;

R⁴ is methyl, 1-methylethyl or chloro;

each R⁵ is independently selected from the group consisting of phthalimidyl, —

R⁷—

C(S)N(R⁸)₂ and —

R⁷—

S(O)_tR⁸ (where t is 0 or

     2);

each R⁷ is a direct bond; and

each R⁸ is independently selected from hydrogen or alkyl.

17. The compound of claim 16 selected from the group consisting of the following:

1-(2,4-Dimethyl-benzyl)-6-[4-(4-methylsulfanyl-phenoxy)-phenyl]-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Dimethyl-benzyl)-6-{4-[4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-phenoxy]-phenyl}-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

3-{4-[5-Cyano-1-(2,4-dimethyl-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-phenoxy}-N,N-dimethyl-thiobenzamide; and

6-[3-Chloro-4-(4-methanesulfonyl-phenoxy)-phenyl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile,

or a pharmaceutically acceptable salt of any of the foregoing.

18. The compound of claim 3 wherein R¹ is heteroarylalkyl.

19. The compound of claim 18 wherein:

n is 0 or 1;

m is 0-2;

R¹ is optionally substituted thiazol-5-ylmethyl;

R² is cyano;

R³ is trifluoromethyl;

R⁴ is methyl, 1-methylethyl or chloro;

each R⁵ is independently selected from the group consisting of halo, alkyl, alkenyl or haloalkyl.

20. The compound of claim 19, i.e., namely 1-(2,5-Diethyl-thiazol-4-ylmethyl)-2-oxo-6-(4-phenoxy-phenyl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile, or a pharmaceutically acceptable salt thereof.

21. The compound of claim 2 wherein:

R¹ is aralkyl optionally substituted with one or more substituents independently selected from alkyl, halo or haloalkyl;

each R⁵ is independently selected from the group consisting of halo, nitro, alkyl, alkenyl, haloalkyl, —

R⁷—

CN, —

R⁷—

N(R⁸)₂, —

R⁷—

OR⁸, —

R⁷—

C(O)R¹¹, —

R⁷—

C(O)OR⁸, —

R⁷—

C(O)N(R⁸)₂, —

R⁷—

N(R⁸)C(O)OR¹⁰, —

R⁷—

S(O)_tR⁸ (where t is 0 to

     2) and —

R⁷—

S(O)₂N(R⁸)₂;

R⁶ is a direct bond, a straight or branched alkenylene chain or a straight or branched alkynylene chain;

each R⁷ is independently selected from a direct bond or a straight or branched alkylene chain;

each R⁸ is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl or heterocyclyl;

each R⁹ is a straight or branched alkylene chain optionally substituted by aryl or heteroaryl;

R¹⁰ is alkyl, aryl, aralkyl or cycloalkylalkyl; and

R¹¹ is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heterarylalkyl.

22. The compound of claim 21 wherein:

n is 0;

m is 1 or 2;

R¹ is benzyl optionally substituted with one or more substituents independently selected from alkyl, halo or haloalkyl;

R² is cyano;

R³ is trifluoromethyl;

each R⁵ is independently selected from the group consisting of alkyl, trifluoromethyl, —

R⁷—

OR⁸ and R⁷—

S(O)_tR⁸ (where t is 0 to

     2);

R⁶ is a direct bond;

R⁷ is a direct bond;

R⁸ is hydrogen or alkyl; and

R⁹ is a straight or branched alkylene chain.

23. The compound of claim 22 selected from the group consisting of the following:

1-(2,4-Difluoro-benzyl)-6-(4′

-methanesulfonyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-methanesulfonyl-biphenyl-4-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-ethylsulfanyl-3′

-trifluoromethyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-ethanesulfonyl-3′

-trifluoromethyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-methylsulfanyl-3′

-trifluoromethyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(5′

-methylsulfanyl-3′

-trifluoromethyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-methylsulfanyl-3′

-trifluoromethyl-biphenyl-4-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(5′

-methylsulfanyl-3′

-trifluoromethyl-biphenyl-4-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-methanesulfonyl-3′

-trifluoromethyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-methanesulfonyl-3′

-trifluoromethyl-biphenyl-4-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(3′

-methanesulfonyl-5′

-trifluoromethyl-biphenyl-4-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(3′

-ethanesulfonyl-5′

-trifluoromethyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[3′

-(propane-2-sulfonyl)-5′

-trifluoromethyl-biphenyl-3-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-ethoxy-3′

-methanesulfonyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[5′

-(propane-1-sulfinyl)-3′

-trifluoromethyl-biphenyl-3-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[5′

-(Butane-1-sulfinyl)-3′

-trifluoromethyl-biphenyl-3-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′

-phenylmethanesulfinyl-3′

-trifluoromethyl-biphenyl-3-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(5′

-Cyclopropylmethanesulfinyl-3′

-trifluoromethyl-biphenyl-3-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′

-(propane-1-sulfinyl)-3′

-trifluoromethyl-biphenyl-4-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[5′

-(Butane-1-sulfinyl)-3′

-trifluoromethyl-biphenyl-4-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′

-phenylmethanesulfinyl-3′

-trifluoromethyl-biphenyl-4-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(5′

-Cyclopropylmethanesulfinyl-3′

-trifluoromethyl-biphenyl-4-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(5′

-ethanesulfinyl-3′

-trifluoromethyl-biphenyl-4-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[3′

-(propane-2-sulfinyl)-5′

-trifluoromethyl-biphenyl-4-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[3′

-(propane-1-sulfonyl)-5′

-trifluoromethyl-biphenyl-3-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[3′

-(propane-1-sulfonyl)-5′

-trifluoromethyl-biphenyl-4-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[3′

-(Butane-1-sulfonyl)-5′

-trifluoromethyl-biphenyl-3-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-[3′

-(Butane-1-sulfonyl)-5′

-trifluoromethyl-biphenyl-4-yl]-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-(3′

-phenylmethanesulfonyl-5′

-trifluoromethyl-biphenyl-3-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-(3′

-phenylmethanesulfonyl-5′

-trifluoromethyl-biphenyl-4-yl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(3′

-Cyclopropylmethanesulfonyl-5′

-trifluoromethyl-biphenyl-3-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(3′

-Cyclopropylmethanesulfonyl-5′

-trifluoromethyl-biphenyl-4-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(3′

-ethanesulfonyl-5′

-trifluoromethyl-biphenyl-4-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[3′

-(propane-2-sulfonyl)-5′

-trifluoromethyl-biphenyl-4-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(5′

-isopropyl-3′

-methanesulfonyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(5′

-ethyl-3′

-methanesulfonyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(3′

-ethanesulfonyl-5′

-isopropyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and

1-(2,4-Difluoro-benzyl)-6-(3′

-methanesulfonyl-5′

-trifluoromethyl-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile,

or a pharmaceutically acceptable salt of any of the foregoing.

24. The compound of claim 21 wherein:

n is 0;

m is 1 or 2;

R¹ is benzyl optionally substituted with one or more substituents independently selected from alkyl, halo or haloalkyl;

R² is cyano;

R³ is trifluoromethyl;

each R⁵ is independently selected from the group consisting of alkyl, —

R⁷—

C(O)R¹¹, —

R⁷—

C(O)OR⁸ or —

R⁷—

C(O)N(R⁸)₂;

R⁶ is a direct bond;

each R⁷ is a direct bond;

each R⁸ is independently hydrogen, alkyl, aryl or aralkyl; and

R¹¹ is hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, pyrrolidinyl or piperidinyl.

25. The compound of claim 24 selected from the group consisting of the following:

6-(3′

-Acetyl-biphenyl-3-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(4′

-Acetyl-biphenyl-3-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-3-carboxylic acid amide;

3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-carboxylic acid amide;

3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-3-carboxylic acid dimethylamide;

3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-carboxylic acid dimethylamide;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[3′

-(pyrrolidine-1-carbonyl)-biphenyl-3-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[4′

-(piperidine-1-carbonyl)-biphenyl-3-yl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-3-carboxylic acid ethylamide;

3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-carboxylic acid methylamide;

3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-carboxylic acid phenylamide;

3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-carboxylic acid benzylamide;

{3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-3-yl}-acetic acid;

{4′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-3-yl}-acetic acid;

{3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-yl}-acetic acid;

{4′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-yl}-acetic acid;

{3-Chloro-3′

-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-yl}-acetic acid methyl ester; and

{3-Chloro-3′

-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-biphenyl-4-yl}-acetic acid,

or a pharmaceutically acceptable salt of any of the foregoing.

26. The compound of claim 21 wherein:

n is 0;

m is 0-2;

R² is cyano;

R³ is trifluoromethyl;

each R⁵ is independently selected from the group consisting of halo, alkyl, alkenyl, haloalkyl or —

R⁷—

OR⁸;

R⁶ is a direct bond, a straight or branched alkenylene chain or a straight or branched alkynylene chain;

R⁷ is a direct bond; and

R⁸ is hydrogen or alkyl.

27. The compound of claim 26 selected from the group consisting of the following:

6-(3′

,5′

-Bis-trifluoromethyl-biphenyl-3-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(3′

,5′

-Bis-trifluoromethyl-biphenyl-4-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(3′

-Chloro-4′

-ethoxy-biphenyl-3-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(3′

,4′

-dimethoxy-biphenyl-4-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(3′

-Chloro-4′

-ethoxy-biphenyl-4-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-(3-phenylethynyl-phenyl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-(4-phenylethynyl-phenyl)-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-2-oxo-6-[3-((E)-styryl)-phenyl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and

1-(2,4-Difluoro-benzyl)-2-oxo-6-[4-((E)-styryl)-phenyl]-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile,

or a pharmaceutically acceptable salt of any of the foregoing.

28. The compound of claim 21 wherein:

n is 0;

m is 1 or 2;

R² is cyano;

R³ is trifluoromethyl;

each R⁵ is independently selected from the group consisting of nitro, —

R⁷—

N(R⁸)₂, —

R⁷—

OR⁸ or —

R⁷—

N(R⁸)C(O)OR¹⁰;

R⁶ is a direct bond;

each R⁷ is a direct bond;

each R⁸ is independently selected from hydrogen or alkyl; and

R¹⁰ is alkyl.

29. The compound of claim 28 selected from the group consisting of the following:

6-(3′

-Amino-biphenyl-3-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

1-(2,4-Difluoro-benzyl)-6-(4′

-ethoxy-3′

-nitro-biphenyl-3-yl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile;

6-(3′

-Amino-4′

-ethoxy-biphenyl-3-yl)-1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile; and

{3′

-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-4-ethoxy-biphenyl-3-yl}-carbamic acid tert-butyl ester,

or a pharmaceutically acceptable salt of any of the foregoing.

30. A method of reducing cholesterol levels in a subject in need thereof, comprising administering an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

31. A method of increasing cholesterol efflux from cells of a subject, comprising administering an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

32. A method of increasing the expression of ATP-Binding Cassette (ABC1) in the cells of a subject, comprising administering an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

33. A method of reducing cholesterol levels in a subject in need thereof, comprising administering an effective amount of a compound of claim 1.

34. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1.