BROMODOMAIN INHIBITORS

• US 20150158873A1
• Filed: 12/09/2014
• Published: 06/11/2015
• Est. Priority Date: 12/09/2013
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Incorporated
• Inventors: Bogdan, Andrew, Kati, Warren M., McDaniel, Keith F., Park, Chang H., Sheppard, George S., Wang, Le
• Granted Patent: US 9,428,514 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4433 containing a six-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/16 Masculine contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• 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 27/02 : Ophthalmic agents
• 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 35/02 : specific for leukemia
• 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 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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 211/86 : Oxygen atoms
• CPC Class Codes: C07D 213/69 : Two or more oxygen atoms
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems

Abstract

The present invention provides for compounds of formula (I)

wherein Y¹, Y², R¹, R², R³, A¹, A², A³, and A⁴, have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein

R¹ is methyl.

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein

R³ is O—

C₁-C₆ alkyl.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein

Y¹ is CR⁴.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein

L is O and G² is phenyl, C₃-C₆ cycloalkyl, or C₄-C₆ heterocycle, each of which is optionally substituted with 1, 2, 3, 4, or 5 R^2g groups.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein

A² is CR⁵, and A¹, A³, and A⁴ are CR⁶.

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein

R⁵ is N(R^5d)-C₁-C₆ alkylenyl-R^5a, N(R^5d)C(O)—

C₁-C₆ alkylenyl-R^5b, N(R^5d)SO₂—

C₁-C₆ allcylenyl-R^5c, or N(R^5d)C(O)N(R^5d)-G¹.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein

R¹ is methyl;

Y¹ is CR⁴; and

R³ is —

O—

C₁-C₃ alkyl.

9. The compound of claim 8 or a pharmaceutically acceptable salt thereof, wherein

A² is CR⁵, and A¹, A³, and A⁴ are CR⁶.

10. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein

L is O ;

and

G² is phenyl or C₃-C₆ cycloalkyl;

each of which is optionally substituted with 1, 2, 3, 4, or 5 R^2g groups.

11. The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein

R⁵ is N(R^5d)—

C₁-C₆ alkylenyl-R^5a, N(R^5d)C(O)—

C₁-C₆ alkylenyl-R^5b, N(R^5d)SO₂—

C₁-C₆ alkylenyl-R^5c, or N(R^5d)C(O)N(R^5d)-G¹.

12. The compound of claim 11 or a pharmaceutically acceptable salt thereof, wherein

R⁴ is H;

and

G² is phenyl which is optionally substituted with 1, 2, or 3 R^2g groups.

13. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein

R⁵ is N(R^5d)—

C₁-C₆ alkylenyl-R^5a.

14. The compound of claim 13 or a pharmaceutically acceptable salt thereof, wherein

R^5d is H or SO₂R⁵′

; and

R^5a is G¹.

15. The compound of claim 13 or a pharmaceutically acceptable salt thereof, wherein

R^5d is SO₂R^5aa;

R^5aa is C₁-C₃ alkyl or (C₁-C₃ alkylenyl)-G¹; and

R^5a is G¹;

wherein G¹ is phenyl, naphthyl, C₃-C₆ cycloalkyl, heteroaryl, or heterocycle;

each of which is optionally substituted.

16. The compound of claim 13 or a pharmaceutically acceptable salt thereof, wherein

R^5d is SO₂R^5aa;

R^5aa is (C₁-C₃ alkylenyl)-G¹ wherein G¹ is optionally substituted phenyl; and

R^5a is G¹;

wherein G¹ is optionally substituted phenyl or optionally substituted cyclopropyl.

17. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein

R⁵ is N(R^5d)C(O)—

C₁-C₆ alkylenyl-R^5b.

18. The compound of claim 17 or a pharmaceutically acceptable salt thereof, wherein

R^5d is H, C₁-C₃ alkyl, or —

(C₁-C₆ alkylenyl)-G¹;

R^5b is G¹, —

OR^5aa, —

S(O)₂R^5aa, —

NR^5bbC(O)R^5dd, —

NR^5bbS(O)₂R^5dd, —

C(O)R^5aa, or —

C(O)NR^5bbR^5cc;

R^5aa, R^5cc, and R^5dd are each independently optionally substituted phenyl or optionally substituted benzyl; and

R^5bb is H or C₁-C₃ alkyl.

19. The compound of claim 17 or a pharmaceutically acceptable salt thereof, wherein

R^5d is H;

and

R^5b is G¹ wherein G¹ is phenyl, naphthyl, C₃-C₆ cycloalkyl, heterocycle, or heteroaryl, each of which is optionally substituted.

20. The compound of claim 17 or a pharmaceutically acceptable salt thereof, wherein R^5d is H;

and

R^5b is G¹ wherein G¹ is optionally substituted phenyl or optionally substituted C₅-C₆ heteroaryl.

21. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein

R⁵ is N(R^5d)C(O)N(R^5d)-G¹.

22. The compound of any one of claims 9-21, or a pharmaceutically acceptable salt thereof, wherein

R⁶ is H.

23. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of

2-(2-chloro-5-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(3,4-dihydro-2H-chromen-6-yl)acetamide;

2-(4-chloro-2-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(1-methyl-1H-pyrazol-4-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(6-methylpyridin-3-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(1,5-dimethyl-1H-pyrazol-3-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(2-methyl-1,3-thiazol-5-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-[3-(2-fluorophenyl)-1H-pyrazol-1-yl]acetamide;

5-[2-(2,4-difluorophenoxy)-5-{[3-(1H-pyrazol-1-yl)propyl] amino}phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

5-{2-(2,4-difluorophenoxy)-5-[(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-2-ylmethyl)amino]phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[2-(2,4-difluorophenoxy)-5-{[(6-methylpyridin-2-yl)methyl]amino}phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[2-(2,4-difluorophenoxy)-5-{[(3-methylpyridin-2-yl)methyl]amino}phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[2-(2,4-difluorophenoxy)-5-{[(1-methyl-1H-pyrazol-5-yl)methyl]amino}phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

methyl 4-{[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]amino}butanoate;

1-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(3-phenoxyphenyl)urea;

1-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(2,4-dimethylphenyl)urea;

1-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(3,5-dimethylphenyl)urea;

1-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea;

1-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(2,5-dimethylphenyl)urea;

1-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(4-fluorophenyl)urea;

1-(3-chlorophenyl)-3-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]urea;

1-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(3-methoxyphenyl)urea;

5-{2-(2,4-difluorophenoxy)-5-[(1,3-oxazol-5-ylmethyl)amino]phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[2-(2,4-difluorophenoxy)-5-{[(1-methyl-1H-imidazol-5-yl)methyl]amino}phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[2-(2,4-difluorophenoxy)-5-{[(1-ethyl-1H-pyrazol-3-yl)methyl]amino}phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-5-oxo-5-phenylpentanamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(phenylsulfonyl)propanamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(3-phenoxyphenyl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-[4-(methylsulfonyl)phenyl]acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-phenoxypropanamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(naphthalen-1-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-{[(4-methylphenyl)sulfonyl]amino}acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(4-methylphenoxy)acetamide;

N-[b 4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(2,3,4-trimethoxyphenyl)propanamide;

2-(benzyloxy)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

2-(1,2-benzoxazol-3-yl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(4-phenoxyphenyl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-4-phenylbutanamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(naphthalen-2-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N′

-phenylpentanediamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-phenylpropanamide;

2-(biphenyl-4-yl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-4-oxo-4-phenylbutanamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-4-phenoxybutanamide;

2-[4-(benzyloxy)phenyl]-N-4-[2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(2-methoxyphenyl)acetamide;

N-(2-{[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]amino}-2-oxoethyl)benzamide;

2-cyclohexyl-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

2-[(1S,4R)-bicyclo[2.2.1]hept-2-yl]-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

5-[5-{[2-(benzyloxy)-3-methoxybenzyl]amino}-2-(2,4-difluorophenoxy)phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[5-{[4-(benzyloxy)benzyl]amino}-2-(2,4-difluorophenoxy)phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

5-{5-[(4-tert-butylbenzyl)amino]-2-(2,4-difluorophenoxy)phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

5-{5-[(2,6-difluorobenzyl)amino]-2-(2,4-difluorophenoxy)phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[2-(2,4-difluorophenoxy)-5-{[3-(4-methoxyphenoxy)benzyl]amino}phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[5-({[5-(2-chlorophenyl)furan-2-yl]methyl}amino)-2-(2,4-difluorophenoxy)phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

4-({[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]amino}methyl)benzonitrile;

2-({[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]amino}methyl)benzonitrile;

5-{2-(2,4-difluorophenoxy)-5-[(quinolin-4-ylmethyl)amino]phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

5-[5-{[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyl]amino}-2-(2,4-difluorophenoxy)phenyl]-4-ethoxy-1-methylpyridin-2(1H)-one;

5-{2-(2,4-difluorophenoxy)-5-[({5-[2-(trifluoromethyl)phenyl]furan-2-yl}methyl)amino]phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

5-{5-[(4-butoxybenzyl)amino]-2-(2,4-difluorophenoxy)phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

5-{2-(2,4-difluorophenoxy)-5-[(4-phenoxybenzyl)amino]phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

3-({[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]amino}methyl)benzonitrile;

5-{2-(2,4-difluorophenoxy)-5-[(4-fluorobenzyl)amino]phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

5-{5-[(cyclopropylmethyl)amino]-2-(2,4-difluorophenoxy)phenyl}-4-ethoxy-1-methylpyridin-2(1H)-one;

1-(2-chloro-5-fluorophenyl)-N-(cyclopropylmethyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]methanesulfonamide;

2-(2-chloro-5-fluorophenyl)-N-(cyclopropylmethyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

N-[4-(benzyloxy)benzyl]-2-(2-chloro-5-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

2-(2-chloro-5-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-(4-fluorobenzyl)acetamide;

2-(2-chloro-5-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]propanamide;

2-(2-chloro-5-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-methylacetamide;

N-(cyclopropylmethyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]ethanesulfonamide;

N-benzyl-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]ethanesulfonamide;

N-(2-chlorobenzyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-(2-phenylethyl)ethanesulfonamide;

N-(cyclopropylmethyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenylmethanesulfonamide;

N-benzyl-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenylmethanesulfonamide;

N-(2-chlorobenzyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenylmethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenyl-N-(2-phenylethyl)methanesulfonamide;

N-[2-(2-chlorophenyl)ethyl]-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(3-phenyl-1H-pyrazol-1-yl)acetamide;

2-(5-chloro-2-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(2-methyl-1,3-thiazol-4-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(1H-pyrazol-1-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(pyrimidin-5-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(3,5-dimethyl-1H-pyrazol-1-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(1H-1,2,4-triazol-1-yl)acetamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-2-(pyrazin-2-yl)acetamide;

N-[2-(2-chlorophenyl)ethyl]-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenylmethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenyl-N-(1,3-thiazol-2-ylmethyl)methanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-(pyridin-3-ylmethyl)ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenyl-N-(pyridin-3-ylmethyl)methanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-(pyrimidin-5-ylmethyl)ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenyl-N-(pyrimidin-5-ylmethyl)methanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-(pyrazin-2-ylmethyl)ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-phenyl-N-(pyrazin-2-ylmethyl)methanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-[(1-methyl-1H-pyrazol-4-yl)methyl]ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-[(1-methyl-1H-pyrazol-4-yl)methyl]-1-phenylmethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-(1,3-thiazol-2-ylmethyl)ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-[(1-methyl-1H-imidazol-4-yl)methyl]ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-[(1-methyl-1H-imidazol-4-yl)methyl]-1-phenylmethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-[(2S)-1,4-dioxan-2-ylmethyl]ethanesulfonamide;

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-(tetrahydro-2H-pyran-4-ylmethyl)ethanesulfonamide; and

N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-N-[2-(tetrahydro-2H-pyran-4-yl)ethyl]ethanesulfonamide.

24. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.

25. A method for treating cancer in a subject comprising administering a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

26. The method of claim 25 wherein the cancer is selected from the group consisting of:

acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute t-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing'"'"'s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin'"'"'s and non-Hodgkin'"'"'s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, leukemia, lymphoma, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom'"'"'s macroglobulinemia, testicular tumors, uterine cancer and Wilms'"'"' tumor.

27. A method for treating a disease or condition in a subject comprising administering a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein said disease or condition is selected from the group consisting of Addison'"'"'s disease, acute gout, ankylosing spondylitis, asthma, atherosclerosis, Behcet'"'"'s disease, bullous skin diseases, cardiac myopathy, chronic obstructive pulmonary disease (COPD), Crohn'"'"'s disease, dermatitis, eczema,giant cell arteritis, glomerulonephritis, heart failure, hepatitis, hypophysitis, inflammatory bowel disease,), Kawasaki disease, lupus nephritis, multiple sclerosis, myocarditis,myositis, nephritis, organ transplant rejection, osteoarthritis, pancreatitis, pericarditis, Polyarteritis nodosa, pneumonitis, primary biliary cirrhosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, scleritis, sclerosing cholangitis, sepsis systemic lupus erythematosus, Takayasu'"'"'s Arteritis, toxic shock, thyroiditis, type I diabetes, ulcerative colitis, uveitis, vitiligo, vasculitis, and Wegener'"'"'s granulomatosis.

28. A method for treating a disease or condition in a subject comprising administering a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein said disease or condition is selected from the group consisting of:

diabetic nephropathy, hypertensive nephropathy, HIV-associated nephropathy, glomerulonephritis, lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis, membranous glomerulonephritis, minimal change disease, polycystic kidney disease and tubular interstitial nephritis.

29. A method for treating an acquired immunodeficiency syndrome (AIDS) in a subject comprising administering a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

30. A method for treating a disease or condition in a subject comprising administering a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein said disease or condition is selected from the group consisting of:

obesity, dyslipidemia, hypercholesterolemia, Alzheimer'"'"'s disease, metabolic syndrome, hepatic steatosis, type II diabetes, insulin resistance, diabetic retinopathy and diabetic neuropathy.

31. A method of contraception in a male subject comprising administering a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable acceptable salt thereof, to a subject in need thereof.

32. A method for treating an acute kidney disease or condition in a subject comprising administering a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein said acute kidney disease or condition is selected from the group consisting of:

ischemia-reperfusion induced kidney disease, cardiac and major surgery induced kidney disease, percutaneous coronary intervention induced kidney disease, radio-contrast agent induced kidney disease, sepsis induced kidney disease, pneumonia induced kidney disease, and drug toxicity induced kidney disease.

33. A method of treating a chronic kidney disease or condition in a subject comprising administering a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein said disease or condition is selected from the group consisting of:

diabetic nephropathy, hypertensive nephropathy, HIV-associated nephropathy, glomerulonephritis, lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis, membranous glomerulonephritis, minimal change disease, polycystic kidney disease and tubular interstitial nephritis.