Triazolopyridine carboxamide derivatives and triazolopyrimidine carboxamide derivatives, preparation thereof and therapeutic use thereof

Abstract

The disclosure relates to the triazolopyridine carboxamide derivatives and triazolopyrimidine carboxamide derivatives of general formula (I): wherein X, A, R 1 and R 2 are as defined herein. The invention further relates to preparation methods and therapeutic use thereof.

1 . A method of treating a pathological condition in a patient in which endogenous 2-arachidonoylglycerol (2-AG) and endogenous 1(3)-arachidonoylglycerol or any other substrate metabolized by the monoacyl glycerol lipase (MGL) enzyme are involved comprising administering to said patient a therapeutically effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         in which: 
         A and X are, independently of one another, nitrogen or CH; 
         R 1  is an aryl or heteroaryl group optionally substituted with one or more groups selected from halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy and halo(C 1 -C 6 )alkoxy; and 
         R 2  is an aryl group optionally substituted with one or more groups selected from halogen, methyl, trifluoromethyl, methoxy and trifluoromethoxy; or 
         a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method according to  claim 1 , wherein for the compound of formula (I):
 A is nitrogen; and   X is CH.   
     
     
         3 . The method according to  claim 1 , wherein for the compound of formula (I):
 R 1  is an aryl or heteroaryl group optionally substituted with one or more groups selected from halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy and halo(C 1 -C 6 )alkoxy.   
     
     
         4 . The method according to  claim 1 , wherein for the compound of formula (I):
 R 1  is phenyl, furan, thiophene or naphthalene, optionally substituted with halogen.   
     
     
         5 . The method according to  claim 1 , wherein the compound is selected from the group consisting of:
 [5-(2-chlorophenyl)[1,2,3]triazolo[4,5-b]pyridin-3-yl][4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   [5-(3-chlorophenyl)[1,2,3]triazolo[4,5-b]pyridin-3-yl][4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   [5-(4-chlorophenyl)[1,2,3]triazolo[4,5-b]pyridin-3-yl][4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   (5-furan-3-yl[1,2,3]triazolo[4,5-b]pyridin-3-yl)[4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   (5-thiophen-3-yl[1,2,3]triazolo[4,5-b]pyridin-3-yl)[4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   (5-naphthalen-2-yl[1,2,3]triazolo[4,5-b]pyridin-3-yl)[4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone; and   (5-naphthalen-1-yl[1,2,3]triazolo[4,5-b]pyridin-3-yl)[4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone.   
     
     
         6 . A method of treating a pathological condition in a patient in which endogenous anandamide or any other substrate metabolized by the Fatty Acid Amide Hydrolase (FAAH) enzyme is involved comprising administering to said patient a therapeutically effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         in which: 
         A and X are, independently of one another, nitrogen or CH; 
         R 1  is an aryl or heteroaryl group optionally substituted with one or more groups selected from halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy and halo(C 1 -C 6 )alkoxy; and 
         R 2  is an aryl group optionally substituted with one or more groups selected from halogen, methyl, trifluoromethyl, methoxy and trifluoromethoxy; or 
         a pharmaceutically acceptable salt thereof. 
       
     
     
         7 . The method according to  claim 6 , wherein for the compound of formula (I):
 A is nitrogen; and   X is CH.   
     
     
         8 . The method according to  claim 6 , wherein for the compound of formula (I):
 R 1  is an aryl or heteroaryl group optionally substituted with one or more groups selected from halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy and halo(C 1 -C 6 )alkoxy.   
     
     
         9 . The method according to  claim 6 , wherein for the compound of formula (I):
 R 1  is phenyl, furan, thiophene or naphthalene, optionally substituted with halogen.   
     
     
         10 . The method according to  claim 6 , wherein the compound is selected from the group consisting of:
 [5-(2-chlorophenyl)[1,2,3]triazolo[4,5-b]pyridin-3-yl][4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   [5-(3-chlorophenyl)[1,2,3]triazolo[4,5-b]pyridin-3-yl][4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   [5-(4-chlorophenyl)[1,2,3]triazolo[4,5-b]pyridin-3-yl][4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   (5-furan-3-yl[1,2,3]triazolo[4,5-b]pyridin-3-yl)[4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   (5-thiophen-3-yl[1,2,3]triazolo[4,5-b]pyridin-3-yl)[4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone;   (5-naphthalen-2-yl[1,2,3]triazolo[4,5-b]pyridin-3-yl)[4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone; and   (5-naphthalen-1-yl[1,2,3]triazolo[4,5-b]pyridin-3-yl)[4-(3-trifluoromethylphenyl)piperazin-1-yl]methanone.   
     
     
         11 . A method of treating a disease selected from the group consisting of an inflammatory disease, dizziness, eating disorders, metabolic syndrome, dyslipidemia, epilepsy, a sleep disorder, osteoporosis, an ocular condition, a pulmonary condition, a gastrointestinal disease, urinary incontinence, and bladder inflammation, comprising administering to said patient a therapeutically effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         in which: 
         A and X are, independently of one another, nitrogen or CH; 
         R 1  is an aryl or heteroaryl group optionally substituted with one or more groups selected from halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy and halo(C 1 -C 6 )alkoxy; and 
         R 2  is an aryl group optionally substituted with one or more groups selected from halogen, methyl, trifluoromethyl, methoxy and trifluoromethoxy; or 
         a pharmaceutically acceptable salt thereof. 
       
     
     
         12 . The method according to  claim 11  wherein the disease is an inflammatory disease. 
     
     
         13 . The method according to  claim 11  wherein the disease is dizziness. 
     
     
         14 . The method according to  claim 11  wherein the disease is selected from the group consisting of eating disorders, metabolic syndrome and dyslipidemia. 
     
     
         15 . The method according to  claim 11  wherein the disease is selected from the group consisting of epilepsy and a sleep disorder. 
     
     
         16 . The method according to  claim 11  wherein the disease is osteoporosis. 
     
     
         17 . The method according to  claim 11  wherein the disease is selected from the group consisting of an ocular condition and a pulmonary condition. 
     
     
         18 . The method according to  claim 11  wherein the disease is selected from the group consisting of a gastrointestinal disease, urinary incontinence and bladder inflammation.