2-{[N-(2-amino-3-(heteroaryl or aryl) propionyl)-aminoacyl]-amino}-alkylboronic acid derivatives

Abstract

The present invention relates to compounds of formula I wherein the substituents are as defined in the description, to processes for the preparation thereof, to pharmaceutical preparations comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

1 - 20 . (canceled)  
   
   
       21 . A pharmaceutical composition for the treatment of a proliferative disease in warm-blooded animals, including humans, comprising, in a dose effective against said disease, a compound according to formula I  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is unsubstituted or substituted aryl; arylalkylcarbonyl, wherein the aryl moiety is unsubstituted or substituted; unsubstituted or substituted heterocyclyl; or heterocyclylalkylcarbonyl, wherein the heterocyclyl moiety is unsubstituted or substituted;  
 R 2  is unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl;  
 R 3  is hydrogen, unsubstituted or substituted aryl or alkyl which is unsubstituted or substituted by 
 unsubstituted or substituted cycloalkyl,  
 unsubstituted or substituted aryl, or  
 unsubstituted or substituted heteroaryl comprising at least one nitrogen atom;  
 
 R 4  is a moiety of the formula IA,  
                     
 wherein A 1  and A 2  are hydroxy or substituted hydroxy, or together with the binding boron atom and the two binding oxygen atoms form a ring of the formula IA*,  
                     
 wherein W is alkylene, substituted alkylene, unsubstituted or substituted cycloalkylene, unsubstituted or substituted bicycloalkylene or unsubstituted or substituted tricycloalkylene;  
 and R 5  is unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted cycloalkyl;  
 or a pharmaceutically acceptable salt of such a compound, together with a pharmaceutically acceptable carrier,  
 wherein the proliferative disease is selected from psoriasis, restenosis, muscle protein degradation or other diseases connected with intracellular protein degradation or negative nitrogen balance, sepsis, burns, trauma, chronic or systemic infections, neuromotor degenerative disease, muscular dystrophia, acidosis, spinal or nerve injuries, diseases related to antigen presentation on cells; and diseases related to cell adhesion.  
 
   
   
       22 . A method of treating warm-blooded animals, including humans, which comprises administering to such warm-blooded animal suffering from a proliferative disease a dose, effective against said disease, of a compound according to formula I  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is unsubstituted or substituted aryl; arylalkylcarbonyl, wherein the aryl moiety is unsubstituted or substituted; unsubstituted or substituted heterocyclyl; or heterocyclylalkylcarbonyl, wherein the heterocyclyl moiety is unsubstituted or substituted;  
 R 2  is unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl;  
 R 3  is hydrogen, unsubstituted or substituted aryl or alkyl which is unsubstituted or substituted by 
 unsubstituted or substituted cycloalkyl,  
 unsubstituted or substituted aryl, or  
 unsubstituted or substituted heteroaryl comprising at least one nitrogen atom;  
 
 R 4  is a moiety of the formula IA,  
                     
 wherein A 1  and A 2  are hydroxy or substituted hydroxy, or together with the binding boron atom and the two binding oxygen atoms form a ring of the formula IA*,  
                     
 wherein W is alkylene, substituted alkylene, unsubstituted or substituted cycloalkylene, unsubstituted or substituted bicycloalkylene or unsubstituted or substituted tricycloalkylene;  
 and R 5  is unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted cycloalkyl;  
 or of a pharmaceutically acceptable salt of such a compound,  
 wherein the proliferative disease is selected from psoriasis, restenosis, muscle protein degradation or other diseases connected with intracellular protein degradation or negative nitrogen balance, sepsis, burns, trauma, chronic or systemic infections, neuromotor degenerative disease, muscular dystrophia, acidosis, spinal or nerve injuries, diseases related to antigen presentation on cells; and diseases related to cell adhesion.