Novel compounds useful in pain management

Abstract

Compounds of the formula I are disclosed and claimed in the present application, as well as their pharmaceutically acceptable salts, pharmaceutical compositions comprising the novel compounds and their use in therapy, particular in the management of pain, and more particularly in the management of pain during labor.

1 . A compound of the formula I  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is selected from 
 (i) linear or branched C 1 -C 6  alkyl;  
 (ii) C 1 -C 6  alkoxy;  
 
 R 2  is selected from 
 (i) hydrogen;  
 (ii) linear or branched C 1 -C 6  alkyl;  
 (iii) C 1 -C 6  alkoxy;  
 
 R 3  and R is each and independently selected from 
 (i) hydrogen;  
 (ii) linear or branched C 1 -C 6  alkyl;  
                     
 
 R 5 , R 6 , R 7 , R 8  and R 9  is each and independently selected from 
 (i) hydrogen;  
 (ii) halogen, where “halogen” encompasses chloro, fluoro, bromo and iodo; and  
 (iii) linear or branched C 1 -C 6  alkyl; and.  
 
 n is an integer of from 1 to 5;  
 as well as pharmaceutically and pharmacologically acceptable salts thereof.  
 
     
     
         2 . A compound of formula I according to  claim 1 , wherein 
 R is a linear C 1 -C 6  alkyl;    R 2  is a linear C 1 -C 6  alkyl or hydrogen;    R 3  and R 4  is each and independently selected from a straight C 1 -C 6  alkyl or hydrogen;    R 5 , R 6 , R 7 , R 8  and R 9  is each and independently selected from 
 (i) hydrogen;  
 (ii) halogen, where “halogen” encompasses chloro, fluoro, bromo and iodo;  
 (iii) linear or branched C 1 -C 6  alkyl; and  
   n is an integer of from 1 to 5.    
     
     
         3 . A compound according to  claim 1 , wherein 
 R 1  is CH 3 ;    R 2  is hydrogen or CH 3 ;    R 3  and R 4  are both hydrogen; and    R 5 , R 6 , R 7 , R 8  and R 9  are all hydrogen; and    n is 4.    
     
     
         4 . A compound according to  claim 1 , which compound is selected from anyone of H-Dmt-D-Arg-Phe-Lys-NH 2 ; 
 H-Dmt-D-Arg-Phe-Om-NH 2 ;    H-Dmt-D-Arg-Phe-A 2 bu-NH 2 ;    H-Mmt-D-Arg-Phe-Lys-NH 2 ;    H-Dmt-D-Arg-Phe(p-F)-Lys-NH 2 ; and    Dmt(NMe)-D-Arg-Phe-Lys-NH 2 .    
     
     
         5 . A compound according to any one of the previous claims, in form of its hydrochloride salt, acetate salt or trifluoroacetate salt.  
     
     
         6 . A compound according to any of claims  1 - 5  for use in therapy.  
     
     
         7 . A compound according to  claim 6 , wherein the therapy is pain management.  
     
     
         8 . A compound according to  claim 7 , wherein the pain is labor pain.  
     
     
         9 . Use of a compound according to formula I of  claim 1 , for the manufacture of a medicament for use in the treatment of pain.  
     
     
         10 . Use according to  claim 9 , wherein the pain is labor pain.  
     
     
         11 . A pharmaceutical composition comprising a compound of the formula I according to  claim 1  as an active ingredient, in admixture with one or more pharmacologically and pharmaceutically acceptable carriers.  
     
     
         12 . A pharmaceutical composition according to  claim 1  1, suitable for administration intrathecally, epidurally, intramuscularly, and intravenously.  
     
     
         13 . A pharmaceutical composition according to  claim 12 , wherein the intravenous administration is by infusion.  
     
     
         14 . A process for the preparation of a compound of the formula I according to  claim 1  by means of solid-phase synthesis, wherein the coupling step in which a protected amino acid is added to the growing peptide chain is performed in an inert solvent using a coupling reagent.  
     
     
         15 . A method for the treatment of a subject suffering from pain, whereby an effective amount of a compound of the formula I of  claim 1 , is administered to a patient in need of pain relief.  
     
     
         16 . A method for treatment according to  claim 15 , wherein the pain is labor pain.