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

摘要

alpha -ketoamide compounds useful for treating disorders mediated by 20S proteasome in mammals having the following formula: wherein X2 is Ar or Ar-X3 wherein X3 is -C=O, or -CH2CO-, and wherein Ar is phenyl, substituted phenyl, indole, substituted indoles, and any other heteroaryls; R1, and R2 are each individually selected from the side chains of the known natural alpha -amino acids and unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear, branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle substituted heterocycle, heteroaryl and substituted heteroaryl; X1 is selected from hydroxide, monoalkylamino, dialkylamino, alkoxide, arylkoxide and wherein X4 is hydroxide, arylamino, monoalkylamino, dialkylamino, alkoxide, or arylalkoxide; and R3 is selected from the known natural alpha -amino acids, unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear and branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle, substituted heterocycle, heteroaryl and substituted heteroaryl.