Optically pure calpain inhibitor compounds

Details Optically pure calpain inhibitor compounds Optically pure calpain inhibitor compounds

1993-06-24

1996-07-30

Nucker, Christine M.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

4 to 5 amino acid residues in defined sequence

530331, 544106, A61K 3804, C07K 500

Patent

active

055412904

ABSTRACT:
Optically pure .alpha.-ketoamide compounds, and use therefor in treating neurodegenerative pathologies having enhanced Calpain activity, are disclosed. These compounds comprise optically pure .alpha.-ketoamides, and physiologically acceptable salts thereof, wherein the .alpha.-ketoamide contains an amino acid isomer which has an L-configuration about the chiral center which is structurally located in the .alpha. position to the ketone of the .alpha.-ketoamide, and wherein the amide functionality of the .alpha.-ketoamide portion of the compound's molecule is derived from an amine of an amino acid or an amine substituted with a sulfone functionality. The method of treating a human neurodegenerative pathology, having enhanced Calpain activity, with a Calpain inhibitor composition while reducing undesirable inhibition of other cysteine proteases and other side effects associated with the racemic calpain inhibitor composition includes administering an optically pure L-isomer of an .alpha.-ketoamide compound, wherein the L-isomer is substantially free of its D-isomer. The method of forming an optically pure L-.alpha.-ketoamide includes mixing an L-.beta.-amino-.alpha.-hydroxyamide in a solution containing a free radical catalyst and then mixing an oxidizing agent into said solution under conditions sufficient to form said optically pure L-.alpha.-ketoamide.

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