Sulfated Benzimidazolone Derivatives Having Mixed Serotonine Receptor Affinity

Abstract

The present invention pertains to a compound of formula (I) wherein R 1 , R 2 , R 3 , and R 4 are each hydrogen or sulfate monoester with the proviso that R 1 , R 2 , R 3 , and R 4 cannot simultaneously be hydrogen, processes for their preparation and their use as pharmaceuticals in the treatment of CNS disorders.

1 . Compounds of general formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 2 , R 3 , and R 4  denote hydrogen or sulfate monoester with the proviso that R 1 , R 2 , R 3 , and R 4  cannot simultaneously represent hydrogen, or a pharmacologically acceptable salt thereof. 
       
     
     
         2 . Compounds of general formula (I) according to  claim 1  wherein two or three of the four radicals R 1 , R 2 , R 3 , and R 4  denote hydrogen. 
     
     
         3 . Compound according to  claim 1  or  2 , selected form the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmacalogically acceptable salt thereof. 
     
     
         4 . Process for the preparation of compounds of general formula (I) according to one or more of  claims 1  to  3 , characterized in that a compound of general formula (II) 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3  and R 4  denote hydroxy or hydrogen and at least one among R 1 , R 2 , R 3  and R 4  is hydroxy, is reacted with a sulfation reagent. 
       
     
     
         5 . Process for the preparation of compounds of general formula (I) according to one or more of  claims 1  to  3 , characterized in that a compound of general formula (III), 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3  and R 4  denote protected sulfate monoester or hydrogen and at least one among R 1 , R 2 , R 3  and R 4  is a protected sulfate monoester, is reacted with a cleavage reagent to restore the free acid moiety. 
     
     
         6 . Compound of formula (I) according to one or more of  claims 1  to  3  for use as a medicament. 
     
     
         7 . Pharmaceutical compositions comprising as an active ingredient a compound of formula (I) according to one or more of  claims 1  to  3  in admixture with one or more pharmaceutical carriers, diluents or excipients. 
     
     
         8 . Use of a compound of formula (I) according to one or more of  claims 1  to  3 , optionally in form of the pharmacologically acceptable salts thereof for preparing a medicament for preventing and/or treating diseases in which the use of therapeutic effective amounts of compounds displaying affinity for the 5-HT 1A  and 5-HT 2 -receptor may have a therapeutic benefit. 
     
     
         9 . Use of a compound of formula (I) according to one or more of  claims 1  to  3 , optionally in form of the pharmacologically acceptable salts thereof for preparing a medicament for preventing and/or treating sexual disorders. 
     
     
         10 . Use according to  claim 9  wherein the sexual disorder is selected from the group consisting of Sexual Desire Disorders, Sexual Arousal Disorders, Orgasmic Disorders, Sexual Pain Disorders, Sexual Dysfunction due to a General Medical Condition, Substance-Induced Sexual Dysfunction, and Sexual Dysfunction not otherwise specified. 
     
     
         11 . Use according to  claim 10  wherein the Sexual Desire Disorder is Hypoactive Sexual Desire Disorder. 
     
     
         12 . Use of a compound of formula (I) according to one or more of  claims 1  to  3 , optionally in form of the pharmacologically acceptable salts thereof for preparing a medicament for preventing and/or treating premenstrual disorders.