Compounds as cannabinoid receptor ligands and uses thereof

1. A compound of formula (I),

or a pharmaceutically acceptable salt thereof, wherein

X is S;

R 1 is

phenyl substituted with 1, 2, 3, 4, or 5 substituents as represented by N,

R j at each occurrence is independently alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfinylalkyl, alkyl-S(O) 2 —, alkyl-S(O) 2 -alkyl-, cyanoalkyl, formyl, ═N—O(alkyl), ═N—OH, alkylthio, alkylthioalkyl, alkynyl, carboxy, carboxyalkyl, cyano, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, nitro, R h R k —N—, (R m R n N)carbonyl, cycloalkyloxy, cycloalkylalkoxy, or cycloalkyl;

R 2 is n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl (3-methylbutyl), neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, n-decyl, alkoxy-(C 2 -C 6 alkylene)-, alkoxyalkoxy-(C 2 -C 6 alkylene)-, alkenyl, alkynyl, cycloalkylalkyl, cycloalkyloxyalkyl, cycloalkylalkoxyalkyl, cyanoalkyl, nitroalkyl, haloalkyl, haloalkoxyalkyl, hydroxyalkyl, R a R b N—(C 2 -C 6 alkylene)-, R c S—(C 2 -C 6 alkylene)-, R c —SO 2 -alkylene-, R c —C(O)-alkylene-, R d C(═N—OR f )—(C 2 -C 6 alkylene)-, R d R e N—SO 2 -alkylene-, or R d R e N—C(O)-alkylene-;

R 3 and R 4 are each independently hydrogen, alkyl, cycloalkyl, haloalkyl, or hydroxyalkyl or R 3 and R 4 taken together with the carbon atom to which they are attached form a monocyclic cycloalkyl;

R 5 and R 6 are each independently hydrogen, alkyl, aryl, cycloalkyl, haloalkyl, or hydroxyalkyl; or

R 5 and R 6 taken together with the carbon atom to which they are attached form a monocyclic cycloalkyl ring; or

R 3 and R 5 taken together with the atoms to which they are attached form a monocyclic cycloalkyl;

R a and R b , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylcarbonyl, arylsulfonyl, or cycloalkyl;

R c , at each occurrence, is independently alkyl, haloalkyl, aryl, or arylalkyl;

R d and R e , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, aryl, or arylalkyl;

R f is hydrogen, alkyl, or haloalkyl;

R h and R k , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylcarbonyl, arylsulfonyl, or cycloalkyl; and

R m and R n , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, aryl, or arylalkyl.

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

R 5 and R 6 are each independently hydrogen, alkyl, or aryl;

R 3 and R 4 are each independently hydrogen or alkyl; and

R 2 is n-butyl, sec-butyl, iso-butyl, or tert-butyl.

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

R 5 and R 6 are each independently hydrogen, alkyl, or aryl;

R 3 and R 4 are each independently hydrogen or alkyl; and

R 2 is alkoxy-(C 2 -C 6 alkylene)-.

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

R 5 and R 6 are each independently hydrogen, alkyl, or aryl;

R 3 and R 4 are each independently hydrogen or alkyl; and

R 2 is cycloalkylalkyl.

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

R 5 and R 6 are each independently hydrogen, alkyl, or aryl;

R 3 and R 4 are each independently hydrogen or alkyl; and

R 2 is n-pentyl, isopentyl (3-methylbutyl), neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, or 2,3-dimethylpentyl.

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

5-chloro-2-methoxy-N-[(2Z)-3-(2-methoxyethyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]benzamide;

N-[(2Z)-3-butyl-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-tert-butyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-tert-butyl-1,3-thiazolidin-2-ylidene]-4-chloro-2-methoxybenzamide;

4-bromo-N-[(2Z)-3-butyl-5-tert-butyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-tert-butyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-(trifluoromethoxy)benzamide;

N-[(2Z)-3-butyl-5-propyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-ethyl-5-methyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-methyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-(4-fluorophenyl)-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-tert-butyl-5-methyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-tert-butyl-5-methyl-1,3-thiazolidin-2-ylidene]-4-chloro-2-methoxybenzamide;

4-bromo-N-[(2Z)-3-butyl-5-methyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

N-[(2Z)-3-butyl-1-thia-3-azaspiro[4.4]non-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-1-thia-3-azaspiro[4.5]dec-2-ylidene]-5-chloro-2-methoxybenzamide;

trans-N-[(2Z)-3-butyl-4,5-dimethyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

cis-N-[(2Z)-3-butyl-4,5-dimethyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(2,4-difluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(3-fluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-isobutyl-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(cyclobutylmethyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

N-[(2Z)-3-butyl-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-(trifluoromethoxy)benzamide;

4-bromo-N-[(2Z)-3-butyl-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

N-[(2Z)-3-butyl-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-4-chloro-2-methoxybenzamide;

trans-N-[(2Z)-3-butylhexahydro-1,3-benzothiazol-2(3H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-methyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide

N-[(2Z)-3-butyl-5-isopropyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2Z)-3-butyl-5-ethyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

5-chloro-N-[(2Z)-5,5-dimethyl-3-neopentyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

N-[(2Z)-3-butyl-5,5-diethyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(2-fluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(2,6-difluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(4-fluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-5,5-dimethyl-3-pentyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(3,4-difluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(2,5-difluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(3,5-difluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-5,5-dimethyl-3-(3-methylbutyl)-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-3-(2,3-difluorobenzyl)-5,5-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

5-chloro-N-[(2Z)-5,5-dimethyl-3-(4,4,4-trifluorobutyl)-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide;

N-[(6Z)-7-butyl-5-thia-7-azaspiro[3.4]oct-6-ylidene]-5-chloro-2-methoxybenzamide;

4-bromo-N-[(6Z)-7-butyl-5-thia-7-azaspiro[3.4]oct-6-ylidene]-2-methoxybenzamide;

N-[(2Z)-3-butyl-4,4-dimethyl-1,3-thiazolidin-2-ylidene]-5-chloro-2-methoxybenzamide; and

4-bromo-N-[(2Z)-3-butyl-4,4-dimethyl-1,3-thiazolidin-2-ylidene]-2-methoxybenzamide.

7. 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.