Discovery of a N′-hydroxyphenylformamidine derivative HET0016 as a potent and selective 20-HETE synthase inhibitor

被引：31

作者：

Sato, M ^{[1
]}

Ishii, T ^{[1
]}

Kobayashi-Matsunaga, Y ^{[1
]}

Amada, H ^{[1
]}

Taniguchi, K ^{[1
]}

Miyata, N ^{[1
]}

Kameo, K ^{[1
]}

机构：

[1] Taisho Pharmaceut Co Ltd, Med Res Labs, Saitama, Saitama 3308530, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 23期

关键词：

D O I：

10.1016/S0960-894X(01)00614-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-(4-Butyl-2-methylphenyl)-N'-hydroxyformamidine (HET0016) was evaluated as the first potent and selective inhibitor of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) synthase. The IC50 value of HET0016 for the production of 20-HETE from arachidonic acid (AA) by human renal microsomes was 8.9 +/- 2.7 nM, with over 200 times the selectivity of xenobiotic-metabolizing cytochrome P450 enzymes. An examination of the structure-activity relationship revealed that the unsubstituted hydroxyformamidine moiety and the substituent at the para-position of the N-hydroxyformamidine moiety are necessary for the potent activity of HET0016. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：2993 / 2995

页数：3

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