Zeneca Limited

Ici Americas, Inc.

Mark M Stein

Diane A Trainor

Richard A Wildonger

Philip D Edwards

John A Schwartz

Cyrus J Ohnmacht

Janet Marie Forst

Robert J Harris

Donald J Wolanin

Andrew Shaw

Scott H Bergeson

The invention concerns pharmaceutically useful trifluoromethyl ketone substituted di-, tri- and tetra-peptide derivatives of the formulae Ia, Ib, Ic set out hereinafter, and salts thereof which are inhibitors of human leukocyte elastase. Also described herein are pharmaceutical compositions containing a peptide derivative and processes and intermediates for use in the manufacture of the peptide derivatives.

Peptide derivatives

The invention concerns pharmaceutically useful trifluoromethyl ketone substituted di-, tri- and tetra-peptide derivatives of the formulae Ia, Ib, Ic set out hereinafter, and salts thereof, which are inhibitors of human leukocyte elastase. Also described herein are pharmaceutical compositions containing a peptide derivative and processes and intermediates for use in the manufacture of the peptide derivatives.

Methods of treating asthma are provided which methods comprise administering to a mammal in need of such treatment an effective amount of a compound of Formula I ##STR1## or a pharmaceutically acceptable salt thereof wherein R.sup.2, R.sup.3, R.sup.4, R.sup.10 and R.sup.11 have any of the meanings given in the specification.

Heterocyclic derivatives

Compounds of formula I ##STR1## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.10 and R.sup.11 have any of the meanings given in the specification, and their pharmaceutically acceptable salts are useful in the treatment of urinery incontinence. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

1-alkyl-2-hydroxy-2-trifluoromethyl ethylamines

Aminoalcohol intermediates for peptide derivatives

The invention relates to selected difluoro compounds of formulae Ia, Ib and Ic (set out hereinafter) which are useful as inhibitors of human leukocyte elastase.

Difluoro keto compounds and their use as HLE inhibitors

The invention discloses a series of difluoroketone, mono- di- and tri-peptide derivatives of formula Ia, Ib and Ic:

Growing community of inventors

Wilmington, DE, United States of America

Mark M Stein