Novel piperidine derivatives

Abstract

wherein A1, A2 and R1 to R3 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

1 - 20 . (canceled) 
     
     
         21 . A method of treating a condition mediated by cysteine protease cathepsin S in a subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of at least one compound of formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof, wherein 
         R 1  is selected from the group consisting of haloalkylsulfonyl, haloalkyl, alkylsulfonyl, phenylalkylsulfonyl, halogen and alkyl; 
         R 2  is hydrogen or halogen; 
         R 3  is hydrogen or halogen; 
         A 1  is heterocyclyl or substituted heterocyclyl, wherein heterocyclyl is selected from the group consisting of 1H-imidazolyl, 1H-[1,2,4]triazolyl, thiazolyl, oxazolyl and 1H-pyrazolyl, and wherein substituted heterocyclyl is heterocyclyl substituted with one or two substituents independently selected from the group consisting of alkyl, phenyl, phenylalkyl and alkoxyalkyl; 
         A 2  is heterocyclyl or substituted heterocyclyl, wherein heterocyclyl is selected from the group consisting of oxodihydroquinazolinyl, oxodihydrobenzoimidazolyl, 1H-pyrrolopyridine, oxodihydroindolyl, benzoimidazol-1-yl, 3-oxo-4H-benzo[1,4]oxazinyl, oxo-1H-imidazolyl, benzo[d]isoxazolyl, oxo-4H-[1,2,4]triazolyl, oxo-5H-imidazopyridinyl and oxopiperidinyl, and wherein substituted heterocyclyl is heterocyclyl substituted with one or two substituents independently selected from the group consisting of alkyl, halogen, alkoxycarbonylalkyl, alkoxyalkyl, pyrrolidinyl, hydroxyalkyl, alkylcarbonyloxyalkyl, alkylsulfonylalkyl, morpholinyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, alkylpiperazinyl, halophenyl and carboxyalkyl. 
       
     
     
         22 . The method of  claim 21 , wherein R 1  is haloalkylsulfonyl, haloalkyl or alkylsulfonyl. 
     
     
         23 . The method of  claim 22 , wherein R 1  is trifluoromethylsulfonyl, trifluoromethyl or methyl sulfonyl. 
     
     
         24 . The method of  claim 21 , wherein R 2  is hydrogen or chloro. 
     
     
         25 . The method of  claim 21 , wherein R 4  is hydrogen. 
     
     
         26 . The method of  claim 21 , wherein A 1  is alkylthiazolyl, heterocyclyl or substituted heterocyclyl, wherein heterocyclyl is selected from the group consisting of 1H-imidazolyl, 1H-[1,2,4]triazolyl, oxazolyl and 1H-pyrazolyl and wherein substituted heterocyclyl is heterocyclyl substituted with one or two substituents independently selected from the group consisting of alkyl, phenyl, phenylalkyl and alkoxyalkyl. 
     
     
         27 . The method of  claim 21 , wherein A 1  is alkyl-1H-imidazolyl or dialkyl-1H-imidazolyl. 
     
     
         28 . The method of  claim 21 , wherein A 1  is selected from the group consisting of methyl-1H-imidazolyl, propyl-1H-imidazolyl and dimethyl-1H-imidazolyl. 
     
     
         29 . The method of  claim 21 , wherein A 2  is selected from the group consisting of oxodihydroquinazolinyl, alkyloxodihydrobenzoimidazolyl, (alkylpyrrolidinyl)oxodihydrobenzoimidazolyl and 1H-pyrrolopyridine. 
     
     
         30 . The method of  claim 21 , wherein A 2  is selected from the group consisting of oxodihydroquinazolinyl, methyloxodihydrobenzoimidazolyl, (methylpyrrolidinyl)oxodihydrobenzoimidazolyl and 1H-pyrrolopyridine. 
     
     
         31 . The method of  claim 21 , wherein A 2  is oxodihydrobenzoimidazolyl substituted with halogen. 
     
     
         32 . The method of  claim 21 , wherein
 R 1  is trifluoromethyl;   R 2  is hydrogen;   R 3  is hydrogen; and   A 1  is 1H-imidazolyl substituted with methyl.   
     
     
         33 . The method of  claim 21 , wherein
 R 1  is trifluoromethyl;   R 2  is hydrogen;   R 3  is hydrogen;   A 1  is 1H-imidazolyl substituted with methyl; and   A 2  is oxodihydrobenzoimidazolyl substituted with one or two substituents independently selected from the group consisting of alkyl, halogen, alkoxycarbonylalkyl, alkoxyalkyl, pyrrolidinyl, hydroxyalkyl, alkylcarbonyloxyalkyl, alkylsulfonylalkyl, morpholinyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, alkylpiperazinyl, halophenyl and carboxyalkyl.   
     
     
         34 . The method of  claim 21  selected from the group consisting of:
 3-{1-[5-Methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[1,5-Dimethyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[2-(4-Methanesulfonyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[5-Methyl-2-(4-phenylmethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-7-fluoro-3,4-dihydro-1H-quinazolin-2-one; 
 (6-Chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-acetic acid methyl ester; 
 1-(2-Methoxy-ethyl)-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[2-(3-Fluoro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 5-Chloro-3-ethyl-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[5-Methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo[3,2-c]pyridine; 
 1-Methyl-3-{1-[5-methyl-2-(4-phenylmethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 1-{1-[2-(4-Methanesulfonyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 7-Fluoro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 1-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-6-pyrrolidin-1-yl-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 5-Chloro-3-methyl-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 6-Bromo-3-[1-[[2-[4-(trifluoromethyl)phenyl]-1H-imidazol-5-yl]methyl]-4-piperidyl]-1,4-dihydroquinazolin-2-one; 
 5-Chloro-3-(2-methoxy-ethyl)-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[5-Benzyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 5-Chloro-3-(2-hydroxy-ethyl)-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 1-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 5-Chloro-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 1-{1-[1,5-Dimethyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 5-Chloro-3-(2-methanesulfonyl-ethyl)-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 Acetic acid 2-(6-chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-ethyl ester; 
 1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[2-(2-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 1-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-6-morpholin-4-yl-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[2-(3,4-Dichloro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[5-Propyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo[2,3-b]pyridine; 
 2-(6-Chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-acetamide; 
 3-{1-[1-(2-Methoxy-ethyl)-5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 2-(6-Chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-N-methyl-acetamide; 
 3-{1-[5-(2-Methoxy-ethyl)-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 1-{1-[2-(3-Fluoro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 1-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 5-Chloro-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-indol-2-one; 
 3-{1-[1-Methyl-5-(4-trifluoromethyl-phenyl)-1H-[1,2,4]triazol-3-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 1-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-benzoimidazole; 
 3-{1-[2-(3,4-Dichloro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-7-fluoro-3,4-dihydro-1H-quinazolin-2-one; 
 6-(4-Methyl-piperazin-1-yl)-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 4-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-4H-benzo[1,4]oxazin-3-one; 
 3-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo[2,3-b]pyridine; 
 1-Methyl-3-{1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 5-(4-Bromophenyl)-3-[1-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1H-imidazol-5-yl]methyl]-4-piperidyl]-1H-imidazol-2-one; 
 6-Fluoro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-benzo[d]isoxazole; 
 3-{1-[2-(4-Chloro-3-fluoro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[4-Methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-3-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo[3,2-c]pyridine; 
 3-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-indole; 
 1-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-indol-2-one; 
 1-{1-[2-(3,4-Dichloro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 1-{1-[2-(2-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 1-Methyl-3-{1-[5-propyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 Sodium; (6-chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-acetate; 
 1-Methyl-3-{1-[5-phenyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[2-(2,4-Dichloro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 5-Chloro-1-{1-[2-(3-chloro-4-methyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 5-Chloro-1-{1-[2-(4-chloro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 3-(1-{5-Methyl-2-[4-(2-methyl-propane-1-sulfonyl)-phenyl}-1H-imidazol-4-ylmethyl]-piperidin-4-yl)-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[2-(3,4-Dichloro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo[2,3-b]pyridine; 
 3-{1-[3-Methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 1-Methyl-3-{1-[1-methyl-5-(4-trifluoromethyl-phenyl)-1H-[1,2,4]triazol-3-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 5-(4-Bromophenyl)-2-[1-[[2-[4-(trifluoromethyl)phenyl]-1H-imidazol-5-yl]methyl]-4-piperidyl]-4H-1,2,4-triazol-3-one; 
 1-Methyl-3-{1-[4-methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-3-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 1-{1-[2-(4-Chloro-3-fluoro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[5-(2-Methoxy-ethyl)-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo[3,2-c]pyridine; 
 5-Chloro-1-{1-[2-(3-fluoro-4-methyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 1-[1-[[4-Methyl-2-[4-(trifluoromethyl)phenyl]-1H-imidazol-5-yl]methyl]-4-piperidyl]-5H-imidazo[4,5-c]pyridin-4-one; 
 1-Methyl-3-(1-{5-methyl-2-[4-(2-methyl-propane-1-sulfonyl)-phenyl}-1H-imidazol-4-ylmethyl]-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one; 
 1-[1-[[4-Methyl-2-[4-(trifluoromethyl)phenyl]-1H-imidazol-5-yl]methyl]-4-piperidyl]piperidin-2-one; 
 1-{1-[2-(2,4-Dichloro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 5-Chloro-1-[1-(5-methyl-2-p-tolyl-1H-imidazol-4-ylmethyl)-piperidin-4-yl]-1,3-dihydro-benzoimidazol-2-one; 
 1-[1-[[2-[4-(Trifluoromethyl)phenyl]-1H-imidazol-5-yl]methyl]-4-piperidyl]-5H-imidazo[4,5-c]pyridin-4-one; and 
 5-(4-Bromophenyl)-3-[1-[[2-[4-(trifluoromethyl)phenyl]-1H-imidazol-5-yl]methyl]-4-piperidyl]-1H-imidazol-2-one. 
 
     
     
         35 . The method of  claim 21  selected from the group consisting of:
 3-{1-[5-Methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[1,5-Dimethyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[2-(4-Methanesulfonyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 3-{1-[5-Methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo[3,2-c]pyridine; 
 1-{1-[2-(4-Methanesulfonyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one; 
 3-{1-[5-Propyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one; 
 6-(4-Methyl-piperazin-1-yl)-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one; and 
 3-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo[3,2-c]pyridine. 
 
     
     
         36 . The method of  claim 21 , wherein the condition mediated by cysteine protease cathepsin S is selected from the group consisting of diabetes, atherosclerosis, abdominal aortic aneurysm, peripheral arterial disease, diabetic nephropathy and lupus nephritis.