Merrell Pharmaceuticals, Inc.

Other

Michel J Jung

Joseph P Burkhart

Daniel G Schirlin

Eugene L Giroux

H Michael Kolb

Bernhard Neises

Fritz E Gerhart, Deceased

Brian Walter Metcalf

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of peptidase substrates in which the amide group containing the scissile amide bond of the substrate peptide has been replaced by an activated electrophilic ketone moiety.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.

Peptidase inhibitors

Novel acetylenic derivatives of amines of the following general structure ##STR1## wherein R is hydrogen, alkylcarbonyl wherein the alkyl moiety has from 1 to 4 carbon atoms and is straight or branched, alkoxycarbonyl wherein the alkoxy moiety has from 1 to 4 carbon atoms and is straight or branched or ##STR2## wherein R.sub.3 is hydrogen, a straight or branched lower alkyl group of from 1 to 4 carbon atoms, benzyl or p-hydroxybenzyl; each of R.sub.1 and R.sub.2 is hydrogen, halogen selected from fluorine, chlorine, bromine and iodine or a straight or branched lower alkyl group of from 1 to 4 carbon atoms and may be the same or different with the proviso that when both R.sub.1 and R.sub.2 are halogen R.sub.1 and R.sub.2 are the same; and pharmaceutically acceptable salts and individual optical isomers thereof.

.alpha.-Acetylenic derivatives of histamine and related compounds

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Pfaffenhoffen, France

Michel J Jung