Piperidin-4-yl-azetidine diamides as monoacylglcerol lipase inhibitors

Abstract

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds, and enantiomers, diastereomers, and pharmaceutically acceptable salts thereof, are represented by Formula (I) as follows: wherein Y, Z, and R are defined herein.

1 .- 16 . (canceled) 
     
     
         17 . A compound of Formula (I) 
       
         
           
           
               
               
           
         
         selected from the group consisting of wherein 
         Y is thiazol-2-yl, Z is biphenyl-4-yl, and R is H; 
         Y is isothiazol-5-yl, Z is biphenyl-4-yl, and R is H; 
         Y is thiazol-2-yl, Z is 3-chloro-6-fluoro-benzothien-2-yl, and R is H; 
         Y is thiazol-4-yl, Z is 4-(3-trifluoromethylphenyl)-phenyl, and R is H; 
         Y is thiazol-4-yl, Z is 4-(5-trifluoromethylthien-2-yl)-phenyl, and R is H; 
         Y is thiazol-4-yl, Z is 4-(3-trifluoromethylphenylmethyl)-phenyl, and R is H; 
         Y is thiazol-4-yl, Z is 3-methyl-6-trifluoromethyl-benzothien-2-yl, and R is H; 
         Y is thiazol-2-yl, Z is 2-fluoro-4-phenyl-phenyl, and R is H; 
         Y is thiazol-2-yl, Z is 4-(3-trifluoromethylphenyl)-phenyl, and R is H; 
         Y is thiazol-2-yl, Z is 3-(3-fluorophenyl)-phenyl, and R is H; 
         Y is thiazol-2-yl, Z is 4-(5-trifluoromethylthien-2-yl)-phenyl, and R is H; 
         Y is thiazol-2-yl, Z is 4-(3-trifluoromethylphenylmethyl)-phenyl, and R is H; 
         Y is thiazol-2-yl, Z is 3-methyl-6-trifluoromethyl-benzothien-2-yl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 2-fluoro-4-phenyl-phenyl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 4-(3-trifluoromethylphenyl)-phenyl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 4-(5-trifluoromethylthien-2-yl)-phenyl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 4-(3-trifluoromethylphenylmethyl)-phenyl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 3-methyl-6-trifluoromethyl-benzothien-2-yl, and R is H; 
         Y is thiazol-2-yl, Z is 4-(4-trifluoromethylphenylmethyl)-phenyl, and R is H; 
         Y is thiazol-2-yl, Z is 2-phenyl-benzoxazol-6-yl, and R is H; 
         Y is thiazol-2-yl, Z is 3-chloro-6-trifluoromethyl-benzothien-2-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(4-fluorophenyl)-1H-indol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(3,4-difluorophenyl)-1H-indol-5-yl, and R is H; 
         Y is thiazol-4-yl, Z is 4-(4-trifluoromethylphenylmethyl)-phenyl, and R is H; 
         Y is thiazol-4-yl, Z is 3-chloro-6-trifluoromethyl-benzothien-2-yl, and R is H; 
         Y is thiazol-4-yl, Z is 1-(4-fluorophenyl)-1H-indol-5-yl, and R is H; 
         Y is thiazol-4-yl, Z is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl, and R is H; 
         Y is thiazol-4-yl, Z is 1-(3,4-difluorophenyl)-1H-indol-5-yl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 4-(4-trifluoromethylphenylmethyl)-phenyl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 2-phenyl-benzoxazol-6-yl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 3-chloro-6-trifluoromethyl-benzothien-2-yl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 1-(4-fluorophenyl)-1H-indol-5-yl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 1-(3,4-difluorophenyl)-1H-indol-5-yl, and R is H; 
         Y is 2-fluoro-4-phenyl-phenyl, Z is thiazol-2-yl, and R is H; 
         Y is 1H-pyrrol-2-yl, Z is 2-fluoro-4-phenyl-phenyl, and R is H; 
         Y is 4-(3-trifluoromethylphenyl)-phenyl, Z is thiazol-2-yl, and R is H; 
         Y is 4-(3-trifluoromethylphenyl)-phenyl, Z is thiazol-4-yl, and R is H; 
         Y is 4-(3-trifluoromethylphenyl)-phenyl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is 3-(3-fluorophenyl)-phenyl, Z is thiazol-2-yl, and R is H; 
         Y is 4-(5-trifluoromethyl-thien-2-yl)-phenyl, Z is thiazol-2-yl, and R is H; 
         Y is 4-(5-trifluoromethyl-thien-2-yl)-phenyl, Z is thiazol-4-yl, and R is H; 
         Y is 4-(5-trifluoromethyl-thien-2-yl)-phenyl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is 4-(3-trifluoromethylphenylmethyl)-phenyl, Z is thiazol-2-yl, and R is H; 
         Y is 4-(3-trifluoromethylphenylmethyl)-phenyl, Z is thiazol-4-yl, and R is H; 
         Y is 4-(3-trifluoromethylphenylmethyl)-phenyl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is 3-methyl-6-trifluoromethyl-benzothien-2-yl, Z is thiazol-2-yl, and R is H; 
         Y is 3-methyl-6-trifluoromethyl-benzothien-2-yl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is 4-(4-trifluoromethylphenylmethyl)-phenyl, Z is thiazol-2-yl, and R is H; 
         Y is 4-(4-trifluoromethylphenylmethyl)-phenyl, Z is thiazol-4-yl, and R is H; 
         Y is 4-(4-trifluoromethylphenylmethyl)-phenyl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is 2-phenyl-benzoxazol-6-yl, Z is thiazol-2-yl, and R is H; 
         Y is 3-chloro-6-trifluoromethyl-benzothien-2-yl, Z is thiazol-2-yl, and R is H; 
         Y is 3-chloro-6-trifluoromethyl-benzothien-2-yl, Z is thiazol-4-yl, and R is H; 
         Y is 3-chloro-6-trifluoromethyl-benzothien-2-yl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is 1-(4-fluorophenyl)-1H-indol-5-yl, Z is thiazol-2-yl, and R is H; 
         the compound wherein Y is 1-(4-fluorophenyl)-1H-indol-5-yl, Z is thiazol-4-yl, and R is H; 
         Y is 1-(4-fluorophenyl)-1H-indol-5-yl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl, Z is thiazol-2-yl, and R is H; 
         Y is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl, Z is thiazol-4-yl, and R is H; 
         Y is 1-(4-trifluoromethylphenyl)-1H-indol-5-yl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is 1-(3,4-difluorophenyl)-1H-indol-5-yl, Z is thiazol-2-yl, and R is H; 
         Y is 1-(3,4-difluorophenyl)-1H-indol-5-yl, Z is thiazol-4-yl, and R is H; 
         Y is 1-(3,4-difluorophenyl)-1H-indol-5-yl, Z is 1H-pyrrol-2-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(4-fluorophenyl)-1H-benzimidazol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(4-trifluoromethylphenyl)-1H-benzimidazol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-phenyl-2-methyl-1H-benzimidazol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(4-fluorophenyl)-2-methyl-1H-benzimidazol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(3,4-difluorophenyl)-2-methyl-1H-benzimidazol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(4-trifluoromethylphenyl)-2-methyl-1H-benzimidazol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(5-chloropyridin-2-yl)-1H-indol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 6-trifluoromethyl-benzothien-2-yl, and R is OH; 
         Y is thiazol-2-yl, Z is 1-(2-methylpyridin-4-yl)-1H-indol-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(3,4-difluorophenyl)-1,3-dihydro-3H-benzimidazol-2-on-5-yl, and R is H; 
         Y is thiazol-2-yl, Z is 1-(4-trifluoromethylphenyl)-1,3-dihydro-3H-benzimidazol-2-on-5-yl, and R is H; 
         and pharmaceutically acceptable salt forms thereof 
       
     
     
         18 . A pharmaceutical composition comprising a compound of  claim 17  and at least one of a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient and a pharmaceutically acceptable diluent. 
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the composition is a solid oral dosage form. 
     
     
         20 . The pharmaceutical composition of  claim 18 , wherein the composition is a syrup, an elixir or a suspension.