1,1-and 1,2-disubstituted cyclopropane compounds

Abstract

A compound selected from those of formula (1): wherein: p represents an integer of from 0 to 6 inclusive, n represents an integer of from 0 to 6 inclusive, R 1 , and R 2 represent a group selected from hydrogen, alkyl, aryl and arylalkyl, or R 1 +R 2 form together with nitrogen carrying them saturated, monocyclic, or bicyclic system, X represents a group selected from oxygen, sulphur, a group —CH═CH—, methylene, a group of formula —HC═N—O— and a group of formula —O—CH 2 —CH═CH—, in which groups oxygen is linked to Y of the compounds of formula (I), Y represents a group selected from aryl, heteroaryl, arylalkyl, heteroarylalkyl, —C(O)-A, and —C(S)-A, A represents a group selected from alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and NR 3 R 4 wherein R 3 , and R 4 represent a group selected from hydrogen, alkyl, aryl, and arylalkyl, or R 3 +R 4 form together with nitrogen carrying them monocyclic, or bicyclic (C 3 -C 10 ) system, its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base, and medicinal products containing the same are useful as specific nicotinic ligand of α 4 β 2 receptors.

1 - A method for treating a living animal body, including a human, afflicted with a condition selected from Tourett's Syndrome and mood disorders comprising the step of administering to the living animal body, including a human, an amount of a compound selected from those of formula (I):  
       
         
           
           
               
               
           
         
       
       wherein: 
 p represents an integer of from 0 to 6 inclusive,  
 n represents an integer of from 0 to 6 inclusive,  
 R 1  and R 2 , which may be identical or different, each independently of the other represent a group selected from hydrogen, linear or branched (C 1 -C 6 )alkyl, aryl, and aryl-(C—C 6 )alkyl in which alkyl is linear or branched,  
 X represents a group selected from oxygen, sulphur,  
 Y represents pyridyl,  
 its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base,  
 it also being understood that:  
 aryl denotes phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indanyl, or indenyl, each of those groups being optionally substituted by one or more, identical or different, groups selected from halogen, linear or branched (C 1 -C 6 )alkyl, hydroxy, cyano, nitro, linear or branched (C 1 -C 6 )alkoxy, linear or branched (C 2 -C 7 )acyl, linear or branched (C 1 -C 6 )alkoxycarbonyl, linear or branched (C 1 -C 6 )trihaloalkyl, linear or branched (C 1 -C 6 )trihaloalkoxy, and amino optionally substituted by one or two linear or branched (C 1 -C 6 )alkyl,  
 pyridyl denotes a pyridyl group which is optionally substituted by one or more, identical or different, groups selected from substituents defined hereinbefore for aryl,  
 which is effective for alleviation of the condition.  
 
     
     
         2 - A method of  claim 1 , wherein n is an integer of from 0 to 2 inclusive.  
     
     
         3 - A method of  claim 1 , wherein R 1 , and R 2 , which may be identical or different, each represent hydrogen, or linear or branched (C 1 -C 6 )alkyl.  
     
     
         4 - A method of  claim 1 , wherein X represents oxygen.  
     
     
         5 - A method of  claim 1  wherein the compound is a compound of formula (IA):  
       
         
           
           
               
               
           
         
       
       wherein n, p, X, Y, R 1  and R 2  are as defined for formula (I), its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base.  
     
     
         6 - A method of  claim 1 , wherein the compound is a compound of formula (IB):  
       
         
           
           
               
               
           
         
       
       wherein n, p, X, Y, R 1 , and R 2  are as defined for formula (I), its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base.  
     
     
         7 - A method of  claim 1 , wherein p is an integer having the value 0 or 1.  
     
     
         8 - A method of  claim 6 , wherein p represents 0, or 1, n represents 0, or 1, R 1  and R 2 , which may be identical or different, represent hydrogen, or linear or branched (C 1 -C 6 )alkyl, X represents oxygen, and Y represents pyridyl, its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base.  
     
     
         9 - A method of  claim 5 , wherein p represents 0, or 1, n is an integer of from 0 to 3 inclusive, R 1  and R 2 , which may be identical or different, represent hydrogen, linear or branched (C 1 -C 6 )alkyl, X represents oxygen or sulphur and Y represents pyridyl, (pyridyl being optionally substituted by a group selected from halogen, and linear or branched (C 1 -C 6 )alkyl), its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base.  
     
     
         10 - A method of  claim 1 , wherein the compound is selected from: 
 N,N-dimethyl-1-[(3-pyridyloxy)methyl]cyclopropanamine,    N-methyl-1-[(3-pyridyloxy)methyl]cyclopropanamine,    N,N-dimethyl-1-[(3-pyridylmethoxy)methyl]cyclopropanamine,    N,N-dimethyl-1-[2-(3-pyridyloxy)ethyl]cyclopropanamine,    1-[(3-pyridyloxy)methyl]cyclopropanamine dihydrochloride,    N-methyl-1-{[(6-methyl-3-pyridyl)oxy]methyl} cyclopropanamine hydrochloride,    N-methyl-1-{[(6-chloro-3-pyridyl)oxy]methyl} cyclopropanamine hydrochloride,    N-methyl-1-[(2-pyridylsulphanyl)methyl]cyclopropanamine dihydrochloride,    N-methyl-1-[3-(3-pyridyloxy)propyl]cyclopropanamine dihydrochloride, and    N-methyl-1-[2-(3-pyridyloxy)ethyl]cyclopropanamine fumarate,    its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base.