Means for the modulation of processes mediated by retinoid receptors and compounds useful therefor

Abstract

In accordance with the present invention, there are provided methods to modulate processes mediated by retinoid receptors, employing high affinity, high specificity ligands for such receptors. In one aspect of the present invention, there are provided ligands which are more selective for the retinoid X receptor than is retinoic acid (i.e., rexoids). In another aspect of the present invention, alternative ligands (other than retinoic acid) have been discovered which are capable of inducing retinoic acid receptor mediated processes. In yet another aspect, methods have been developed for the preparation of such retinoid receptor ligands from readily available compounds.

1 .- 29 . (canceled)  
     
     
         30 . A formulation comprising: 
 9-cis-retinoic acid, pharmaceutically acceptable salts thereof, or pharmaceutically acceptable hydrolyzable esters thereof, and    a pharmaceutically acceptable carrier.    
     
     
         31 . The formulation according to  claim 30  wherein said compound is 9-cis-retinoic acid.  
     
     
         32 . The formulation according to  claim 31  wherein said formulation is suitable for oral administration.  
     
     
         33 . The formulation according to  claim 32  wherein the pharmaceutically acceptable carrier is selected from tablets, dispersible powders, granules, syrups, elixirs, sterile aqueous or non-aqueous solutions, suspensions, or emulsions.  
     
     
         34 . The formulation according to  claim 31  wherein said formulation is suitable for intravenous administration.  
     
     
         35 . The formulation according to  claim 34  wherein the pharmaceutically acceptable carrier is selected from dispersible powders, sterile aqueous or non-aqueous solutions, suspensions, or emulsions.  
     
     
         36 . The formulation according to  claim 31  wherein said formulation is suitable for subcutaneous administration.  
     
     
         37 . The formulation according to  claim 36  wherein the pharmaceutically acceptable carrier is selected from dispersible powders, sterile aqueous or non-aqueous solutions, suspensions, or emulsions.  
     
     
         38 . The formulation according to  claim 31  wherein said formulation is suitable for intramuscular administration.  
     
     
         39 . The formulation according to  claim 38  wherein the pharmaceutically acceptable carrier is selected from dispersible powders, granules, sterile aqueous or non-aqueous solutions, suspensions, or emulsions.  
     
     
         40 . The formulation according to  claim 31  wherein said formulation is suitable for intracutaneous administration.  
     
     
         41 . The formulation according to  claim 40  wherein the pharmaceutically acceptable carrier is selected from dispersible powders, granules, sterile aqueous or non-aqueous solutions, suspensions, or emulsions.  
     
     
         42 . The formulation according to  claim 30  wherein the pharmaceutically acceptable carrier is selected from creams, lotions, tablets, dispersible powders, granules, syrups, elixirs, sterile aqueous or non-aqueous solutions, suspensions, or emulsions.  
     
     
         43 . The formulation according to  claim 30  wherein said carrier contains an agent selected from wetting agents, emulsifying and suspending agents, dispersing agents, sweetening agents, flavoring agents or perfuming agents.  
     
     
         44 . The formulation according to  claim 30  wherein said agent is a wetting agent.  
     
     
         45 . The formulation according to  claim 30  wherein said agent is an emulsifying and suspending agent.  
     
     
         46 . The formulation according to  claim 30  wherein said agent is a dispersing agent.  
     
     
         47 . The formulation according to  claim 30  wherein said agent is a sweetening agent.  
     
     
         48 . The formulation according to  claim 30  wherein said agent is a flavoring agent.  
     
     
         49 . The formulation according to  claim 30  wherein said agent is a perfuming agent.  
     
     
         50 . A formulation consisting essentially of: 
 9-cis-retinoic acid, pharmaceutically acceptable salts thereof, or pharmaceutically acceptable hydrolyzable esters thereof, and    a pharmaceutically acceptable carrier.    
     
     
         51 . A formulation consisting of: 
 9-cis-retinoic acid, pharmaceutically acceptable salts thereof, or pharmaceutically acceptable hydrolyzable esters thereof, and    a pharmaceutically acceptable carrier.    
     
     
         52 . A composition in unit dosage form for oral administration comprising as an active ingredient a compound selected from the group consisting of 9-cis retinoic acid, pharmaceutically acceptable salts thereof, pharmaceutically acceptable hydrolyzable esters thereof and a pharmaceutically acceptable carrier suitable for oral administration.  
     
     
         53 . A pharmaceutically acceptable formulation comprising a pharmaceutically acceptable carrier and 9-cis-retinoic acid.  
     
     
         54 . A pharmaceutically acceptable formulation consisting essentially of a pharmaceutically acceptable carrier and 9-cis-retinoic acid.  
     
     
         55 . A pharmaceutically acceptable formulation consisting of a pharmaceutically acceptable carrier and 9-cis-retinoic acid.