.alpha.-ketoamide inhibitors of 20S proteasome

Details .alpha.-ketoamide inhibitors of 20S proteasome .alpha.-ketoamide inhibitors of 20S proteasome

1998-01-26

2000-06-13

Geist, Gary

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

514419, C07D20912, A01N 4338

Patent

active

060751509

ABSTRACT:
.alpha.-ketoamide compounds useful for treating disorders mediated by 20S proteasome in mammals having the following formula: wherein X.sub.2 is Ar or Ar--X.sub.3 wherein X.sub.3 is --C.dbd.O, or --CH.sub.2 CO--, and wherein Ar is phenyl, substituted phenyl, indole, substituted indoles, and any other heteroaryls; R.sub.1, and R.sub.2 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; X.sub.1 is selected from hydroxide, monoalkylamino, dialkylamino, alkoxide, arylkoxide and ##STR1## wherein X.sub.4 is hydroxide, arylamino, monoalkylamino, dialkylamino, alkoxide, or arylalkoxide; and R.sub.3 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.

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