Non-bioconvertible c3-substituted pregnenolone derivatives for use in the treatment of substance use disorders

Abstract

The present invention relates to the use of non-bioconvertible C3-substituted pregnenolone derivatives of formula (I), with no significant affinity for hormonal receptors or receptors of the central nervous system, in the treatment of substance use disorders, and in particular of alcohol use disorder.

1 . A method for treating or preventing relapse of a substance use disorder in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         each of   independently represents a single or a double bond; 
         R 1  represents a C 1 -C 4  alkyl; 
         R 2  represents —CO—; —CH(OH)— or —CH(O—COCH 3 )—; and 
         R 3  represents H or CHCl 2  and R 4  represents H or CH 3 , or R 3  and R 4  together represent 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method of  claim 1 , wherein said compound is of formula (II): 
       
         
           
           
               
               
           
         
         wherein: 
            represents a single or a double bond; 
         R 1  represents a C 1 -C 4  alkyl; 
         R 2  represents —CO— or —CH(OH)—; and 
         R 3  represents H or CHCl 2 . 
       
     
     
         3 . The method of  claim 2 , wherein R 1  is CH 3 . 
     
     
         4 . The method of  claim 2 , wherein   is a double bond. 
     
     
         5 . The method of  claim 2 , wherein R 2  is —CO—. 
     
     
         6 . The method of  claim 2 , wherein R 3  represents H. 
     
     
         7 . The method of  claim 1 , wherein said compound is selected from the following compounds: 
       
         
           
           
               
               
           
         
         and pharmaceutically acceptable salts thereof. 
       
     
     
         8 . The method of  claim 7 , wherein said compound is 3-methoxy-pregna-5-ene-20-one of formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         9 . The method of  claim 1 , wherein said compound is selected from the following compounds: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and pharmaceutically acceptable salts thereof. 
       
     
     
         10 . The method of  claim 9 , wherein said compound is 3β-methoxy-pregna-5-ene-20-one of formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         11 . The method of  claim 1 , wherein
 said substance use disorder is selected from alcohol use disorder; cannabis use disorder; hallucinogens (including phencyclidine, ketamine, and LSD) use disorders; opioids (including codeine, fentanyl, heroin, morphine, opium, methadone, oxycodone, and hydrocodone) use disorders; sedative, hypnotic or anxiolytic medications (including barbiturates and benzodiazepines) use disorders; stimulants (including nicotine, amphetamine, and methylphenidate) use disorders; and inhalants (such as glue, shoe polish, toluene, spray paints, gasoline, and lighter fluid) use disorders.   
     
     
         12 . The method of  claim 11 , wherein said substance use disorder is alcohol use disorder (AUD). 
     
     
         13 . The method of  claim 1 , wherein said compound or pharmaceutically acceptable salt thereof is administered via oral, intravenous, transdermal, subcutaneous, intranasal, topical, sublingual, or rectal route. 
     
     
         14 . The method of  claim 1 , wherein said compound or pharmaceutically acceptable salt thereof is administered at a dose of 50 to 2000 mg/day. 
     
     
         15 . The method of  claim 1 , wherein said compound or pharmaceutically acceptable salt thereof is part of a pharmaceutical composition further comprising at least one pharmaceutically acceptable excipient. 
     
     
         16 . A method for treating or preventing relapse of an alcohol use disorder (AUD) in a subject in need thereof, comprising administering to said patient a therapeutically efficient amount of compound 3β-methoxy-pregna-5-ene-20-one of formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         17 . The method of  claim 16 , wherein said compound or pharmaceutically acceptable salt thereof is administered via oral, intravenous, transdermal, subcutaneous, intranasal, topical, sublingual, or rectal route. 
     
     
         18 . The method of  claim 16 , wherein said compound or pharmaceutically acceptable salt thereof is administered at a dose of 50 to 2000 mg/day. 
     
     
         19 . The method of  claim 16 , wherein said compound or pharmaceutically acceptable salt thereof is part of a pharmaceutical composition further comprising at least one pharmaceutically acceptable excipient. 
     
     
         20 . The method of  claim 11 , wherein said compound is 3β-methoxy-pregna-5-ene-20-one of formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.