PEPTIDE DERIVATIVES BEING ALPHA-KETOAMIDE INHIBITORS OF 20S PROTEASOME, PHARMACEUTICAL COMPOSITIONS COMPRISING THEREOF AND THEIR USE

摘要

The present invention relates to compounds of formula I wherein X2 is -Ar or -Ar-X3, wherein X3 is -C (O) -, -CH2C (O) - or - (CH2) n-. wherein n is a number from 0 to 2 and Ar is phenyl, substituted phenyl, indolyl, substituted indolyl, or any other heteroaryl; R 1 and R 2 independently represent the side chain of known natural α-amino acids and non-natural amino acids, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, substituted aryl, alkoxyaryl, cycloalkyl, heterocyclic, substituted heterocyclyl, heteroaryl or substituted heteroaryl; X1 is hydroxy, monoalkylamino, dialkylamino, alkoxy, aryloxy or a group of the formula wherein X4 is hydroxy, arylamino, monoalkylamino, dialkylamino, alkoxy or arylalkoxy; R3 is a side chain of known natural α-amino acids and non-natural amino acids, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, substituted aryl, alkoxyaryl, cycloalkyl, heterocyclic, substituted heterocyclyl, heteroaryl or substituted heteroaryl. The present invention also encompasses salts of the above compounds, and pharmaceutical compositions containing them, for use in the treatment of cell proliferative disorders, and the use of the above compounds. SHE