Amides that inhibit vanilloid receptor subtype 1 (VR1) receptor

1. A compound of formula (I)

or a pharmaceutically acceptable salt, amide, ester, or prodrug thereof, wherein

A is isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, thiazolyl or thienyl,

X is CH;

Y is CH;

L is —C(O)N(R 3 )—;

R 1 is hydrogen, alkoxy, alkyl, aryloxy, haloalkoxy, haloalkyl, or halogen;

R 2 is hydrogen, alkoxy, alkyl, haloalkoxy, haloalkyl, or halogen; and

R 3 is hydrogen.

2. The compound according to claim 1 wherein

A is isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, thiazolyl or thienyl;

X is CH;

Y is CH; and

L is —C(O)N(R 3 )—.

3. The compound according to claim 1 wherein

A is imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, thiazolyl or thienyl;

X is CH;

Y is CH;

L is —C(O)N(R 3 )—; and R 1 and R 2 are independently hydrogen, alkoxy, alkyl, haloalkoxy, or haloalkyl.

4. The compound according to claim 3 that is

N-(4-tert-butylphenyl)-4-(2-pyridinyl)benzamide;

-(4-tert-butylphenyl)-4-(3-nitro-2-pyridinyl)benzamide;

4-(3-amino-2-pyridinyl)-N-(4-tert-butylphenyl)benzamide;

4-[3-(acetylamino)-2-pyridinyl]-N-(4-tert-butylphenyl)benzamide;

N-(4-tert-butylphenyl)-4-(1,3-thiazol-2-yl)benzamide;

N-(4-tert-butyl phenyl)-4-(2-pyrimidinyl)benzamide;

N-(4-tert-butylphenyl)-4-(3-cyano-2-pyridinyl)benzamide;

N-(4-tert-butylphenyl)-4-(2-thienyl)benzamide;

4-{3-[acetyl(methylsulfonyl)amino]-2-pyridinyl}-N-(4-tert-butylphenyl)benzamide;

4-(6-bromo-2-pyridinyl)-N-(4-ter-t-butylphenyl)benzamide;

ethyl 2-(4-{[(4-tert-butylphenyl)amino]carbonyl}phenyl)-3-pyridinylcarbamate;

4-(3-{bis[(chloromethyl)sulfonyl]amino}-2-pyridinyl)-N-(4-tert-butylphenyl)benzamide;

N-(4-tert-butylphenyl)-4-(2-pyridinyl)benzenesulfonamide;

N-(4-tert-butylphenyl)-4-(1H-pyrazol-1-yl)benzamide;

N-(4-tert-butylphenyl)-4-(3-pyridinyl)benzamide;

N-(4-tert-butylphenyl)-6-(1H-pyrazol-1-yl)nicotinamide;

N-(4-tert-butylphenyl)-4-(4-pyrid inyl)benzamide;

N-(4-tert-butylphenyl)-4-(1,3-oxazol-2-yl)benzamide;

N-(4-tert-butylphenyl )-4-(3-chloro-2-pyridinyl)benzamide;

4-(3-chloro-2-pyridinyl)-N-(3-methylphenyl)benzamide;

4-(3-chloro-2-pyridinyl)-N-(4-methylphenyl)benzamide;

4-(3-chloro-2-pyridinyl)-N-(4-methoxyphenyl)benzamide;

4-(3-chloro-2-pyridinyl)-N-[3-(trifluoromethoxy)phenyl]benzamide;

4-(3-chloro-2-pyridinyl)-N-(3,4-dimethylphenyl)benzamide;

4-(3-chloro-2-pyridinyl)-N-(4-ethylphenyl)benzamide;

4-(3-chloro-2-pyridinyl)-N-(4-isopropylphenyl)benzamide;

N-(4-tert-butylphenyl)-4-[5-(trifluoromethyl)-1H-pyrazol-1-yl]benzamide;

N-[4-(trifluoromethyl)phenyl]-4-[5-(trifluoromethyl)-1H-pyrazol-1-yl]benzamide;

N-(4-tert-butylphenyl)-4-(3-isoxazolyl)benzamide; or

N-(4-tert-butylphenyl)-4-(3-fluoro-2-pyridinyl)benzamide.

5. A compound that is 4-{3- [bis(methylsulfonyl)amino]-2-pyridinyl}-N-(4-tert-butylphenyl)benzamide.

6. A compound that is N-(4-tert-butylphenyl)-4-{3-[(dimethylamino)sulfonyl]-2-pyridinyl}benzamide.

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.