Ici Americas, Inc.

Imperial Chemical Industries Limited

Zeneca Limited

Richard A Wildonger

Diane A Trainor

Philip D Edwards

Mark M Stein

John A Schwartz

Anand Swaroop Dutta

Ross L Stein

Donald J Wolanin

Joseph J Lewis

Andrew Shaw

Anthony F Heald

Charles W Perkins

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

Aminoalcohol intermediates for peptide derivatives

The invention provides a series of novel heterocyclic ketones of formula I ##STR1## and pharmaceutically acceptable base-addition salts thereof, in which the values of R.sup.4, L, A, X and Q have the meanings defined in the following specification. The compounds of formula I are inhibitors of human leukocytic elastase. The invention also provides pharmaceutical compositions containing a compound of formula I, or a pharmaceutically acceptable base-addition salt thereof, and processes and intermediates for the manufacture of compounds of formula I.

Heterocyclic ketones

Proline derivatives

Proline derivatives of the formulae: ##STR1## wherein R.sup.1 through R.sup.11 have defined values, and acid- and base-addition salts thereof, and equilibrium addition compounds of the aldehyde group thereof; processes for their preparation; pharmaceutical compositions; and intermediates for preparing said proline derivatives. The proline derivatives are human leukocyte elastase inhibitors which are useful, for example, in treating pulmonary emphysema.

Certain pyrazolo[3,4-b]pyridine compounds which are useful for their activity in the central nervous system of warm-blooded animals, of the following formula (I) ##STR1## wherein R.sub.1 is lower alkyl;

Pyrazolo[3,4-b]pyridine compounds

Substituted 1-aralkyl-1H-v-triazoles are prepared from a suitable 1-aralkyl-1H-v-triazole by a process comprising an alkylation step and dependent on the product desired suitably followed by an oxidation step and decarboxylation step.

Synthesis of substituted 1-aralkyl-1H-v-triazoles

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Newark, DE, United States of America

Richard A Wildonger