Selective retinoid agonists

Abstract

This invention relates to new RAR selective retinoid agonists of formula I wherein the symbols are as defined in the specification to their pharmaceutically acceptable salts, individual isomers or to a racemic or non-racemic mixture; to pharmaceutical compositions containing them, and to methods for their use as therapeutic agents.

1 . A retinoid, wherein the retinoid is a compound of formula I  
       
         
           
           
               
               
           
         
         wherein  
         the dotted bond is either present and forms a double bond, or is absent;  
         R 1 , R 2 , R 3 , R 4  are independently of each other hydrogen or alkyl;  
         n is 1, 2 or 3;  
         X is R 8 R 9 C< for n=1, 2 or 3; or  
         X is oxygen for n=1;  
         each R 8  and each R 9  is independently hydrogen or alkyl;  
         R 5  is hydrogen, alkyl, alkoxy, alkoxy-alkyl-, alkylthio, alkyl-NR 10 —, alkenyl, alkenyloxy, alkynyl, benzyl, cycloalkyl-alkyl, or phenyl-alkyl;  
         R 10  is hydrogen or alkyl;  
         m is 0 when the dotted bond is present; and  
         m is 1 when the dotted bond is absent; and  
         A is a residue of formula  
         wherein  
         R 7  is hydrogen or alkyl;  
         or when R 7  is hydrogen, a pharmaceutically active salt of the compound.  
       
     
     
         2 . The retinoid according to  claim 1 , wherein each R 8  is the same and each R 9  is the same.  
     
     
         3 . The retinoid according to  claim 2 , wherein each R 8  is hydrogen and each R 9  is hydrogen.  
     
     
         4 - 19 . (canceled)  
     
     
         20 . The retinoid according to  claim 1 , wherein the compound has the formula  
       
         
           
           
               
               
           
         
         wherein  
         the dotted bond is present and forms a double bond, or is absent;  
         R 1 , R 2 , R 3 , R 4  are independently of each other hydrogen or alkyl;  
         n is 1, 2 or 3  
         X is R 8 R 9 C< for n=1, 2 or 3; or  
         X is oxygen for n=1;  
         each R 8  and each R 9  is independently hydrogen or alkyl;  
         R 5  is hydrogen, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, benzyl, cycloalkyl-alkyl, or phenyl-alkyl;  
         m is 0 when the dotted bond is present; or  
         m is 1 when the dotted bond is absent; and  
         R 7  is hydrogen or alkyl;  
         or when R 7  is hydrogen, a pharmaceutically active salt of the compound.  
       
     
     
         21 . The retinoid according to  claim 20 , wherein each R 8  is the same and each R 9  is the same.  
     
     
         22 . The retinoid according to  claim 21 , wherein each R 8  is hydrogen and each R 9  is hydrogen.  
     
     
         23 . The retinoid according to  claim 20 , wherein the compound is 3-methyl-7-(4,4,7,7-tetramethyl-2-pentyl-2,3,4,5,6,7-hexahydro-1H-inden-2-yl)-hepta-2,4,6-trienoic acid.  
     
     
         24 . The retinoid according to  claim 1 , wherein the retinoid is the pharmaceutically acceptable salt of the compound formed from a pharmaceutically acceptable base.  
     
     
         25 . The retinoid according to  claim 24 , wherein the pharmaceutically acceptable salt is an alkali salt, ammonium salt, or substituted ammonium salt.