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Inhibitors of the 26s proteolytic complex and the 20s proteasome contained therein

  • US 5,693,617 A
  • Filed: 01/15/1995
  • Issued: 12/02/1997
  • Est. Priority Date: 03/15/1994
  • Status: Expired due to Fees
First Claim
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1. A method for reducing the rate of loss of muscle mass in an animal comprising contacting cells of the muscle with a proteasome inhibitor of the structure:

  • ##STR93## where P is an amino-group-protecting moiety;

    B1 at each occurrence is independently selected from the group consisting of ##STR94## X is selected from the group consisting of ##STR95## X1 at each occurrence and X2 are independently selected from the group consisting of ##STR96## except that if B1 is ##STR97## then X1 must be ##STR98## R is hydrogen or together with the adjacent R1, or R2 if A=0, forms a nitrogen-containing heterocyclic ring;

    R1 at each occurrence, R2, and R3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, and --CH2 --R4,where R4 is aryl, aralkyl, alkaryl, cycloalkyl or --Y--R5,where Y is a chalcogen, and R5 is alkyl; and

    A is 0, 1, or 2; and

    wherein, stereochemically, B1 --R1 is D, L, or a mixture thereof and CH--R2 and CH--R3 are independently L or a mixture of D and L.

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