Compounds as cannabinoid receptor ligands

1. A compound according to formula (I),

or a pharmaceutically acceptable salt thereof, wherein

n is 0, 1, 2, 3, or 4;

R1, at each occurrence, is independently selected from the group consisting of alkyl, alkoxylalkyl, haloalkyl, hydroxyalkyl, oxo, R4O2C—, RcRdNC(O)—, and RcRdNS(O)2—; two R1 together with the same carbon atom to which they are attached, optionally form a 4-, 5-, or 6-membered monocyclic cycloalkyl;

R2 is selected from the group consisting of aryl, cycloalkyl, heterocycle, and ReRfN—;

R3 is selected from the group consisting of alkyl, alkoxyalkyl, haloalkyl, hydroxyalkyl, R5—C(O)—, R5-C(═N—ORp)—, R6OC(O)—, RgRjNC(O)—, R5-S(O)2—, and RgRjNS(O)2-;

R4 is selected from the group consisting of alkyl, arylalkyl, haloalkyl, and heterocycloalkyl;

R5, at each occurrence, is selected from the group consisting of alkyl, alkoxyalkyl, aryl, cycloalkyl, haloalkyl, heteroaryl, and heterocycle;

R6 is selected from the group consisting of alkyl, arylalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, and heteroarylalkyl;

Rc and Rd, at each occurrence, are each independently selected from the group consisting of hydrogen, alkyl, and haloalkyl, or Rc and Rd together with the nitrogen atom to which they are attached form a heterocyclic ring;

Re is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkylalkyl, and alkylcarbonyl;

Rf is selected from the group consisting of hydrogen, alkyl, and haloalkyl;

Rg, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, and heterocycloalkyl;

Rj, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, and haloalkyl; and

Rp is selected from the group consisting of hydrogen and alkyl.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R3 is R5-C(O)—.

3. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein R2 is aryl.

4. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein R2 is cycloalkyl.

5. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein R2 is heterocycle.

6. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein R2 is ReRfN—.

7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R3 is R6OC(O)—.

8. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein R2 is aryl.

9. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein R2 is cycloalkyl.

10. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein R2 is heterocycle.

11. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R3 is RgRjNC(O)—.

12. The compound according to claim 11 or a pharmaceutically acceptable salt thereof, wherein R2 is cycloalkyl.

13. The compound according to claim 11 or a pharmaceutically acceptable salt thereof, wherein R2 is aryl.

14. The compound according to claim 11 or a pharmaceutically acceptable salt thereof, wherein R2 is heterocycle.

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

ethyl 2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4-methyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-2-fluoro-6-(trifluoromethyl)benzamide;

ethyl 4-methyl-2-{[2-(trifluoromethyl)benzoyl]amino}-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

N-[3-(azetidin-1-ylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-2-fluoro-6-(trifluoromethyl)benzamide;

N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-2-(trifluoromethyl)benzamide;

ethyl 2-{[3-chloro-2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4-methyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

2-fluoro-N-{3-[(3-methoxyazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-6-(trifluoromethyl)benzamide;

N-(3-benzoyl-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl)-2-fluoro-6-(trifluoromethyl)benzamide;

N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-2-fluoro-6-(trifluoromethyl)benzamide;

N-[3-(cyclopropylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-2-fluoro-6-(trifluoromethyl)benzamide;

N-[3-(cyclopentylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-2-fluoro-6-(trifluoromethyl)benzamide;

2-chloro-N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-6-fluorobenzamide;

N-(3-benzoyl-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl)-3-chloro-2-fluoro-6-(trifluoromethyl)benzamide;

N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-N′-(1-cyclopropyl-1-methylethyl)urea;

ethyl 2-[(2,6-difluorobenzoyl)amino]-4-methyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

2-fluoro-N-{3-(2-furoyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-6-(trifluoromethyl)benzamide;

ethyl 2-[(2-chloro-6-fluorobenzoyl)amino]-4-methyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

ethyl 2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

ethyl 2-{[5-chloro-2-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

ethyl 4,4,6,6-tetramethyl-2-{[(2,2,3,3-tetramethylcyclopropyl)carbonyl]amino}-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

ethyl 2-{[(1-methoxybicyclo[2.2.2]oct-2-yl)carbonyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

ethyl 4,4,6,6-tetramethyl-2-({[(1S,2R,4R)-2-methylbicyclo[2.2.1]hept-2-yl]carbonyl}amino)-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

4,4,6,6-tetramethyl-N-propyl-2-{[(2,2,3,3-tetramethylcyclopropyl)carbonyl]amino}-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

ethyl 4-methyl-2-{[(2,2,3,3-tetramethylcyclopropyl)carbonyl]amino}-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

ethyl 4-methyl-2-({[(1S,2R,4R)-2-methylbicyclo[2.2.1]hept-2-yl]carbonyl}amino)-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-2,2,3,3-tetramethylcyclopropanecarboxamide;

5-chloro-N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-2-methoxybenzamide;

2-fluoro-N-{3-[(3-hydroxyazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-6-(trifluoromethyl)benzamide;

N-(3-benzoyl-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl)-2,2,3,3-tetramethylcyclopropanecarboxamide;

N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-2,2,3,3-tetramethylcyclopropanecarboxamide;

N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide;

N-[3-(cyclopropylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide;

N-[3-(cyclopentylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide;

N-[3-(2-furoyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide;

N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-2,2-dimethyl-4-oxo-3,4-dihydro-2H-pyran-6-carboxamide;

N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-2-ethoxybenzamide;

2-chloro-N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-5-fluorobenzamide;

N-[3-(cyclobutylcarbonyl)-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl]-2-(trifluoromethoxy)benzamide;

ethyl 2-[(2,6-dichlorobenzoyl)amino]-4-methyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

ethyl 4-methyl-2-{[2-oxatricyclo[3.3.1.1˜3,7˜]dec-1-ylcarbonyl]amino}-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-2-oxatricyclo[3.3.1.1˜3,7-]decane-1-carboxamide;

N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}hexahydro-2,5-methanopentalene-3a(1H)-carboxamide;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-N-propyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-N-(2-methoxyethyl)-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

ethyl 4-methyl-2-({[(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]hept-1-yl]carbonyl}amino)-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

(1S,4R)-N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide;

ethyl 2-{[5-chloro-2-(trifluoromethyl)benzoyl]amino}-4-methyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

3-chloro-N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-2-fluoro-6-(trifluoromethyl)benzamide;

3-chloro-2-fluoro-N-{3-[(3-methoxyazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-6-(trifluoromethyl)benzamide;

2-fluoro-N-[4-methyl-3-(tetrahydro-2H-pyran-4-ylcarbonyl)-4,6-dihydrothieno[2,3-c]furan-2-yl]-6-(trifluoromethyl)benzamide;

5-chloro-N-{3-[(3,3-difluoroazetidin-1-yl)carbonyl]-4-methyl-4,6-dihydrothieno[2,3-c]furan-2-yl}-2-(trifluoromethyl)benzamide;

ethyl 2-[(2,6-dimethylbenzoyl)amino]-4-methyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-N-(3,3,3-trifluoropropyl)-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

N-cyclobutyl-2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

N-cyclopentyl-2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-N-isobutyl-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-N-[(2S)-tetrahydrofuran-2-ylmethyl]-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

N-(cyclopropylmethyl)-2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-N-[(2R)-tetrahydrofuran-2-ylmethyl]-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

propyl 4,4,6,6-tetramethyl-2-{[2-(trifluoromethyl)benzoyl]amino}-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

propyl 2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-N-isopropyl-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-N-prop-2-ynyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-N-[(2S)-2-hydroxypropyl]-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide;

ethyl 2-{[4-fluoro-2-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

ethyl 2-{[5-fluoro-2-(trifluoromethyl)benzoyl]amino}-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxylate;

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-N-(2-hydroxyethyl)-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide; and

2-{[2-fluoro-6-(trifluoromethyl)benzoyl]amino}-N-(3-hydroxypropyl)-4,4,6,6-tetramethyl-4,6-dihydrothieno[2,3-c]furan-3-carboxamide.

16. 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.

17. A method of treating pain in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.

18. A method for treating nociceptive pain in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.

19. A method for treating neuropathic pain in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.

20. A method for treating a disorder selected from the group consisting of inflammatory disorders, immune disorders, neurological disorders, cancers of the immune system, respiratory disorders, and cardiovascular disorders in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.

21. A method for providing neuroprotection in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.