Peptidase inhibitors
AssigneeMerrell Pharmaceuticals Inc.
InventorsH. Michael Kolb, Joseph P. Burkhart, Michel J. Jung, Fritz E. Gerhart, deceased, Eugene L. Giroux, Bernhard Neises, Daniel G. Schirlin
Life of this patent
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Abstract
This invention relates to analogs of peptidase substrates in which the amide group containing the scissile amide bond of the substrate peptide has been replaced by an activated electrophilic ketone moiety. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states.
Claims7
A compound of the formula ##STR61## the hydrates thereof, and the pharmaceutically acceptable salts thereof useful for inhibiting human leukocyte elastase wherein
- R.sub.2 is the side chain of the .alpha.-amino acids Ala, Leu, Ile, Val, n-Val or n-Leu,
- R.sub.1 is -P.sub.2 P.sub.3 P.sub.4 Pg with P.sub.2 being Pro or Ala,
- P.sub.3 is Ala, Leu, Ile, Val, n-Val, n-Leu or Lys,
- P.sub.4 is Ala or is deleted,
- P.sub.g is an optional terminal moiety selected from Ac, Suc, Bz, Boc, CBZ, DNS, Iva, MeOSuc, AdSO.sub.2, AcAc or 2-CBZ,
- X is X.sub.1 or X.sub.2 wherein
- X.sub.1 is -CF.sub.3, -CF.sub.2 H, -CO2R.sub.3 or -CONHR.sub.3,
- X2 is ##STR62## Y is -OR.sub.3, R.sub.3 is hydrogen, C.sub.1-4 straight or branched alkyl, phenyl, benzyl, cyclohexyl or cyclohexylmethyl, and
- R.sub.5 is deleted, with the proviso that when the R.sub.1 moiety bears a Pro in its P.sub.2 position, then X is other than CF.sub.3.
Dependencies are inferred from the claim text.