Format

Send to

Choose Destination
J Med Chem. 1997 Sep 26;40(20):3173-81.

Orally active trifluoromethyl ketone inhibitors of human leukocyte elastase.

Author information

1
Department of Medicinal Chemistry, ZENECA Pharmaceuticals, A Business Unit of ZENECA Inc., Wilmington, Delaware 19897, USA.

Abstract

This paper describes the development a series of peptidyl trifluoromethyl ketone inhibitors of human leukocyte elastase which are found to have excellent pharmacological profiles. Methods have been developed that allow for the synthesis of these inhibitors in stereochemically pure form. Two of these compounds, 1k and 1l, have high levels of oral bioavailability in several species. Compound 1l has entered development as ZD8321 and is presently undergoing clinical evaluation. These compounds demonstrate that peptidyl trifluoromethyl ketone inhibitors can achieve high levels of oral activity and bioavailability, and therefore they may prove useful as therapeutic agents in the treatment of diseases in which elastase is implicated.

PMID:
9379436
DOI:
10.1021/jm970250z
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center