Peptidyl human heart chymase inhibitors. 2. Discovery of highly selective difluoromethylene ketone derivatives with Glu at P3 site

被引：29

作者：

Eda, M ^{[1
]}

Ashimori, A ^{[1
]}

Akahoshi, F ^{[1
]}

Yoshimura, T ^{[1
]}

Inoue, Y ^{[1
]}

Fukaya, C ^{[1
]}

Nakajima, M ^{[1
]}

Fukuyama, H ^{[1
]}

Imada, T ^{[1
]}

Nakamura, N ^{[1
]}

机构：

[1] Green Cross Res Labs, Dept Med Chem, Hirakata, Osaka 573, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(98)00132-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Appropriate structural modification of the difluoromethylene ketone derivatives at both P3 and P' positions led us to the discovery of peptidyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine protease bovine alpha-chymotrypsin (chymotrypsin Ki = >100 mu M). Using the compound 12b, a docking study with human heart chymase was carried out to presume probable interactions, (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：919 / 924

页数：6

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