New 3-aryl-2-hydroxypropionic acid derivative I

Abstract

A novel 3-aryl-2-hydroxypropionic acid derivative, a process and intermediate for its manufacture, pharmaceutical preparations containing it and the use of the compound in clinical conditions associated with insulin resistance.

1 . A compound having the formula  
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts, solvates, and crystalline forms thereof.  
     
     
         2 . A process for the preparation of a compound according to    claim 1   , characterized by 
 a) converting a compound of the formula II                          wherein A is a chiral auxiliary group or the group —OR p , wherein R p  is a protective group, or    b) reacting a compound of the formula III                          with a compound of the formula IV                          in which formulas A is —OH, a chiral auxiliary group or the group —OR p , wherein R p  is a protective group, X is —OH or a leaving group and Q is H, whereafter, if necessary, hydrolysing the obtained compound, or    c) diastereoisomerically separating a compound of the formula V                          wherein Q is —CH 2 CH 2 Ph—4—OSO 2 CH 3  and A is a chiral auxiliary group, whereafter hydrolysing the obtained compound, or    d) enantiomerically separating a compound of the formula V                          wherein Q is —CH 2 CH 2 Ph—4—OSO 2 CH 3  and A is —OH or —OR p , wherein R p  is a protective group, whereafter, if necessary hydrolysing the obtained compound, or    e) asymmetrically reducing a compound of the formula VII                          wherein Q is —CH 2 CH 2 Ph—4—OSO 2 CH 3  and A is —OH, a chiral auxiliary group or the group —OR p , wherein R p  is a protective group, whereafter, if necessary, hydrolysing the obtained compound, or    f) alkylating a compound of the formula XII                          wherein Q is —CH 2 CH 2 Ph—4—OSO 2 CH 3  and A is —OH, a chiral auxiliary group or the group —OR p , wherein R p  is a protective group, whereafter, if necessary, hydrolysing the obtained compound, or    g) reacting a compound of the formula XV                          with a compound of the formula IX                          in which formulas X is a leaving group, Q is —CH 2 CH 2 Ph—4—OSO 2 CH 3  and A is a chiral auxiliary group used to induce chirality in the product whereafter, hydrolysing the obtained compound, or    h) resolving a racemate of the formula I rac                            whereafter, if desired, the compound obtained according to any of methods a)-h) is converted to a pharmaceutically acceptable salt, and/or a solvate such as a hydrate thereof.    
     
     
         3 . A compound of the formula IV  
       
         
           
           
               
               
           
         
       
       wherein Q is hydrogen and A is —OH, a chiral auxiliary group or the group —OR p , wherein R p  is a protective group.  
     
     
         4 . A compound according to    claim 3   , wherein in formula IV A is —OH or alkoxy having 1 to 3 carbon atoms.  
     
     
         5 . A compound according to    claim 1    for use in therapy.  
     
     
         6 . A pharmaceutical formulation containing a compound according to    claim 1    as active ingredient optionally together with a pharmaceutically acceptable carrier, adjuvant and/or diluent.  
     
     
         7 . The use of a compound according to    claim 1    in the manufacture of a medicament for the prophylaxis and/or treatment of clinical conditions associated with insulin resistance.  
     
     
         8 . A method for the prophylaxis and/or treatment of clinical conditions associated with insulin resistance wherein a therapeutically active amount of a compound according to    claim 1    is administered to a mammal in the need of such prophylaxis and/or treatment.  
     
     
         9 . A method according to    claim 8    wherein the prophylaxis and/or treatment of clinical conditions associated with insulin resistance is the prophylaxis and/or treatment of dyslipidaemia in such conditions.  
     
     
         10 . A method according to    claim 8    wherein the prophylaxis and/or treatment of clinical conditions associated with insulin resistance is the prophylaxis and/or treatment of hyperglycaemia in non insulin dependent diabetes mellitus.  
     
     
         11 . A pharmaceutical formulation for use in the prophylaxis and/or treatment of clinical conditions associated with insulin resistance wherein the active ingredient is a compound according to    claim 1   .