PEPTIDYL HUMAN HEART CHYMASE INHIBITORS - 2 - DISCOVERY OF HIGHLY SELECTIVE DIFLUOROMETHYLENE KETONE DERIVATIVES WITH GLU AT P3 SITE

Authors
EDA M ASHIMORI A AKAHOSHI F YOSHIMURA T INOUE Y FUKAYA C NAKAJIMA M FUKUYAMA H IMADA T NAKAMURA N
Citation
M. Eda et al., PEPTIDYL HUMAN HEART CHYMASE INHIBITORS - 2 - DISCOVERY OF HIGHLY SELECTIVE DIFLUOROMETHYLENE KETONE DERIVATIVES WITH GLU AT P3 SITE, Bioorganic & medicinal chemistry letters, 8(8), 1998, pp. 919-924
Citations number
7
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
8
Year of publication
1998
Pages
919 - 924
Database
ISI
SICI code
0960-894X(1998)8:8<919:PHHCI->2.0.ZU;2-7
Abstract
Appropriate structural modification of the difluoromethylene ketone de rivatives at both P3 and P' positions led us to the discovery of pepti dyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine proteas e bovine alpha-chymotrypsin (chymotrypsin Ki = >100 mu M). Using the c ompound 12b, a docking study with human heart chymase was carried out to presume probable interactions, (C) 1998 Elsevier Science Ltd. All r ights reserved.