Antagonists of the TRPV1 receptor and uses thereof

1. A compound of formula (I)

or a pharmaceutically acceptable salt thereof, wherein

L 1 is a bond;

Y 1 is —N(R b )—;

Y 2 is ═O, ═S or ═N—CN;

Y 3 is —N(R c )—;

Ar 1 is 3,4-dihydro-2H-chromen-2-yl, 3,4-dihydro-2H-chromen-3-yl, or 3,4-dihydro-2H-chromen-4-yl;

wherein each Ar 1 is optionally substituted with 1, 2, 3, 4, or 5 substituents as represented by R w , two R w that are attached to the same carbon atom of the monocyclic heterocycle, together with the carbon atom to which they are attached, optionally form a monocyclic cycloalkyl ring wherein said monocyclic cycloalkyl ring is optionally substituted with 1, 2, or 3 substituents selected from the group consisting of oxo, alkyl, and haloalkyl;

R 1 is hydrogen, hydroxyl or alkoxy;

R w , R 2 , R 3 , R 4 , and R 5 , are each independently hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, hydroxyl, hydroxyalkyl, nitro, R e OS(O) 2 —, R f R g N—, (R f R g N)alkyl, (R j R k N)carbonyl, (R j R k N)carbonylalkyl or (R j R k N)sulfonyl;

R b and R c are each independently hydrogen or alkyl;

R e is alkyl, haloalkyl, aryl, or arylalkyl;

R f and R g , at each occurrence, are each independently hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, arylalkyl, arylcarbonyl, carboxyalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, or heteroarylcarbonyl; or

R f and R g taken together with the nitrogen atom to which they are attached form a heterocyclic ring; and

R j and R k , at each occurrence, are each independently hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonylalkyl, alkyl, alkylcarbonylalkyl, carboxyalkyl, cycloalkylalkyl, haloalkyl, or hydroxyalkyl.

2. The compound according to claim 1 wherein

Y 1 is —N(R b )—;

Y 2 is O; and

Y 3 is —N(R c )—.

3. The compound of claim 1 , wherein

R 1 is hydroxyl;

R 2 is hydrogen, and

Ar 1 is 3,4-dihydro-2H-chromen-3-yl.

4. The compound according to claim 3 wherein Ar 1 is optionally substituted with 1, 2, 3, 4, or 5 substituents as represented by R w and each R w is independently alkoxy, alkyl, arylalkyl, halogen, haloalkyl, or R f R g N— wherein R f and R g are each independently hydrogen, alkyl, or haloalkyl.

5. The compound according to claim 1 , wherein

R 1 is hydroxyl;

R 2 is hydrogen; and

Ar 1 is 3,4-dihydro-2H-chromen-4-yl.

6. The compound according to claim 5 wherein Ar 1 is optionally substituted with 1, 2, 3, 4, or 5 substituents as represented by R w and each R w is independently alkoxy, alkyl, arylalkyl, halogen, haloalkyl, or R f R g N— wherein R f and R g are each independently hydrogen, alkyl, or haloalkyl.

7. A compound selected form the group consisting of:

N-3,4-dihydro-2H-chromen-3-yl-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;

N-(8-tert-butyl-3,4-dihydro-2H-chromen-3-yl)-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;

N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-N′-(7-methoxy-3,4-dihydro-2H-chromen-3-yl)urea;

N-(6-chloro-3,4-dihydro-2H-chromen-3-yl)-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;

N-(8-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;

N-3,4,7,8,9,10-hexahydro-2H-benzo[h]chromen-4-yl-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;

N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-N′-(6-methyl-3,4-dihydro-2H-chromen-4-yl)urea;

N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea; and

N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea.

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

9. The pharmaceutical composition according to claim 8 further including a non-toxic pharmaceutically acceptable carrier and diluent.