Novel 3,3-diphenylpropylamines useful in therapy

Abstract

Novel 3,3-diphenylpropylamines of the formula and any stereoisomers thereof; wherein R 1 represents —H or —CH 3 ; R 2 represents —CX 3 , —CR 2-1 X 2 , —CR 2-1 R 2-2 X, or —CR 2-1 R 2-2 H, wherein X represents halogen, and R 2-1 and R 2-2 independently represent —H or —(C 1 -C 4 alkyl), optionally substituted with halogen; R 3 and R 4 independently represent —H, —OCH 3 , —OH, —CONH 2 , —SO 2 NH 2 , —F, —Cl, —Br, —I, —CF 3 , or —(C 1 -C 4 alkyl), optionally substituted with one or two —OH, —(C 1 -C 4 alkoxy), —COOH, or —CO—O—(C 1 -C 3 alkyl); and R 5 and R 6 independently represent C 1 -C 6 alkyl, optionally substituted with hydroxyl, wherein R 5 and R 6 together contain at least three carbon atoms, and wherein R 5 and R 6 may form a ring together with the amine nitrogen; provided that R 2 comprises at least one halogen; or a physiologically acceptable acid addition salt thereof; the 3,3-diphenylpropylamines for use as medicaments, use of the 3,3-diphenylpropylamines for the manufacture of specific medicaments, and pharmaceutical compositions comprising the 3,3-diphenylpropylamines. The present invention also includes a method of treatment involving administration of the 3,3-diphenylpropylamines.

1 . A 3,3-diphenylpropylamine of the formula  
       
         
           
           
               
               
           
         
       
       and any stereoisomers thereof; 
 wherein R 1  represents 
 —H or —CH 3 ;  
 
 R 2  represents —CX 3 , —CR 2-1 X 2 , —CR 2-1 R 2-2 X, or —CR 2-1 R 2-2 H, wherein X represents halogen, and R 2-1  and R 2-2  independently represent —H or —(C 1 -C 4  alkyl), optionally substituted with halogen;  
 R 3  and R 4  independently represent —H, —OCH 3 , —OH, —CONH 2 , —SO 2 NH 2 , —F, —Cl, —Br, —I, —CF 3 , or —(C 1 -C 4  alkyl), optionally substituted with one or two —OH, —(C 1 -C 4  alkoxy), —COOH, or —CO—O—(C 1 -C 3  alkyl); and  
 R 5  and R 6  independently represent C 1 -C 6  alkyl, optionally substituted with hydroxyl, wherein R 5  and R 6  together contain at least three carbon atoms, and wherein R 5  and R 6  may form a ring together with the amine nitrogen;  
 provided that R 2  comprises at least one halogen;  
 or a physiologically acceptable acid addition salt thereof:  
 
     
     
         2 . A 3,3-diphenylpropylamine according to  claim 1 , wherein the R 2  group is situated opposite the OR 1  group in their common phenyl ring structure.  
     
     
         3 . A 3,3-diphenylpropylamine according to  claim 1 , wherein X represents fluorine.  
     
     
         4 . A 3,3-diphenylpropylamine according to  claim 1 , wherein R 2  represents —CX 3 .  
     
     
         5 . A 3,3-diphenylpropylamine according to  claim 1 , wherein at least one of R 3  and R 4  represents —H.  
     
     
         6 . A 3,3-diphenylpropylamine according to  claim 1 , wherein both R 3  and R 4  represent —H.  
     
     
         7 . A 3,3-diphenylpropylamine according to  claim 1 , wherein at least one of R 5  and R 6  represents C 1 -C 3  alkyl.  
     
     
         8 . A 3,3-diphenylpropylamine according to  claim 7 , wherein said at least one of R 5  and R 6  represents isopropyl.  
     
     
         9 . A 3,3-diphenylpropylamine according to  claim 7 , wherein both R 5  and R 6  represent isopropyl.  
     
     
         10 . A 3,3-diphenylpropylamine according to  claim 1 , wherein the carbon stereocenter is (R).  
     
     
         11 . A 3,3-diphenylpropylamine according to  claim 1 , wherein the carbon stereocenter is (S).  
     
     
         12 . A 3,3-diphenylpropylamine according to  claim 1 , which is present in the form of a mixture of stereoisomers.  
     
     
         13 . A 3,3-diphenylpropylamine according to  claim 1 , which is selected from the group consisting of: 
 N,N-diisopropyl-3-(2-methoxy-5-trifluoromethylphenyl)-3-phenylpropanamine;    N,N-diisopropyl-3-(2-hydroxy-5-trifluoromethylphenyl)-3-phenylpropanamine; and    N,N-diisopropyl-3-(2-hydroxy-5-trifluoromethylphenyl)-3-phenylpropanamine tartrate.    
     
     
         14 . A pharmaceutical composition comprising a therapeutically effective amount of a 3,3-diphenylpropylamine according to any one of claims  1 - 13 , and a suitable pharmaceutical carrier therefor.  
     
     
         15 . A 3,3-diphenylpropylamine according to any one of claims  1 - 13  for use as a medicament.  
     
     
         16 . Use of a 3,3-diphenylpropylamine according to any one of claims  1 - 13  for the manufacture of a medicament for treating urinary disorders.  
     
     
         17 . A method of treating urinary disorders in a mammal, including man, comprising administering to said mammal, in need of such a treatment, a therapeutically effective amount of a 3,3-diphenylpropylamine according to any one of claims  1 - 13 .