Novel compounds and methods of treating cell proliferative diseases, retinopathies and arthritis

Abstract

The present invention relates to compounds and their uses, particularly in the pharmaceutical industry. The invention discloses compounds having anti-proliferative and antiangiogenic activities, as well as methods for treating various diseases associated with abnormal cell proliferation, including cancer, or associated with unregulated angiogenesis including growth and metastasis of solid tumors, ocular diseases and especially retinopathies, or arthritis, by administering said compounds. It further deals with pharmaceutical compositions comprising said compounds, more particularly useful to treat cancers (such as leukemia), ocular diseases and arthritis.

1 . A compound having a general formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  is selected from the group consisting of: 
 
     
       
         
         
             
             
         
       
       R 2  represents a hydrogen atom, an alkyl or alkenyl group containing from 3 to 6 carbon atoms; 
       B represents an halogen atom, preferably chlorine, a hydroxyl group, a —O—CH 2 —O—CH 3  (MOM) group, a —O—CH 2 —O—CH 2 —CH 2 —O—CH 3  (MEM) group, a —OSO 2 -alkyl group or a —OSi(CH 3 ) 2 tBu; 
       D represents an oxygen atom, NR 3 , CR′R″ or a sulfur atom; 
       X represents an oxygen atom, a sulfur atom or a radical —NR 4 —; 
       Y represents an oxygen atom, a sulfur atom or a radical —NR 4 —; 
       R 3  represents a hydrogen, an alkyl group, a carboxylate group, an acyl group, a carboxamide group or a SO 2 -alkyl group; 
       R′ and R″, identical or different, represent a hydrogen atom or an alkyl radical; 
       R 4 , identical or different, is selected from a group consisting of a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms, an aryl and an aralkyl; 
       “linker” represents (CH 2 ) n , wherein n represents an integer between 1 and 10 inclusive, optionally interrupted by an heteroatom (preferably N, O, S and P) or a carbonyl group, or an aryldialkyl (preferably xylenyl) group; 
       A represents a group selected from: 
     
     
       
         
         
             
             
         
       
       optionally A is substituted, 
     
     its tautomers, optical and geometrical isomers, racemates, salts, hydrates and mixtures thereof.