Use of 2-amino-thiazoline derivatives as inhibitors of inducible no-synthase

Abstract

The present invention relates to a process for preparing 2-amino-thiazoline derivatives of formula (II): in which either Y is a methylene (CH 2 ) and X is chosen from the following groups: O, NH, (C1-C4) N-Alkyl, N-Bn, N-Ph, N-(2-Py), N-(3-Py), N-(4-Py), N-2-pyrimidyl, N-5-pyrimidyl, S, SO, SO 2 , CH 2 or CHPh; or Y is a carbonyl (C═O) and X is chosen from the following groups: NH, N-Ph, N-(2-Py), N-(3-Py), N-(4-Py), N-2-pyrimidyl or N-5-pyrimidyl.

1 ) An intermediate compound for the preparation of 2-amino-thiazoline derivatives, said intermediate being selected from the compounds of formulas (IIa), (IIb), and (IIc),  
     
       
         
         
             
             
         
       
       wherein:  
       Ra is a protecting group of the amine function and Rb is a protecting group of the acid function,  
       and in which  
       either Y is a methylene (CH 2 ) and X is selected from O, NH, N—(C1-C4)alkyl, N-Bn, N-Ph, N-(2-Py), N-(3-Py), N-(4-Py), N-2-pyrimidyl, N-5-pyrimidyl, S, SO, SO 2 , CH 2 , and CHPh;  
       or Y is a carbonyl (C═O) and X is selected from: NH, N-Ph, N-(2-Py), N-(-′-Py), N-(4-Py), N-2-pyrimidyl and N-5-pyrimidyl;  
       said (C1-C4)alkyl radicals containing 1 to 4 carbons in a straight or branched chain, 
 and said abbreviations Bn, Py and Ph signifying, respectively, benzyl, pyridyl and phenyl  
 excluding, however, the following compounds:  
 N-[2-hydroxy-1-(4-phenyl-piperazin-1-ylmethyl)ethyl]thiobenzamide,  
 methyl 2-(N-CBZ-amino)-3-morpholino-propionate,  
 boc-DL-β-(4-morpholinyl)alanine methyl ester,  
 methyl 2-acetamido-3-piperidinopropanoate,  
 methyl 2-acetamido-3-morpholinopropanoate,  
 ethyl 2-(N-benzyl-amino)-3-piperidinopropanoate, and  
 ethyl 2-(N-benzyl-amino)-3-morpholinopropanoate.  
 
     
   
   
       2 ) An intermediate compound according to  claim 1 , selected from the group consisting of: 
 N-(tert-Butyl)-N′-[2-hydroxy-1-(4-méthyl-pipérazin-1-ylméthyl)ethyl]-thiourea;    N-[2-Hydroxy-1-(4-méthyl-pipérazin-1-ylméthyl)ethyl]acetamide; and    methyl 2-(Acetylamino)-3-(4-methyl-piperazin-1-yl)propanoate.