Benzene-di-N-octylcarbamates as conformationally constrained phospholipase A2 inhibitors

被引：5

作者：

Lin, G ^{[1
]}

Lin, YF ^{[1
]}

Hwang, MT ^{[1
]}

Lin, YZ ^{[1
]}

机构：

[1] Natl Chung Hsing Univ, Dept Chem, Taichung 402, Taiwan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 03期

关键词：

D O I：

10.1016/j.bmcl.2003.11.047

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

Conformationally constrained 1,2-, 1,3-, and 1,4- benzene-di-N-octylcarbamates are potent reversible competitive inhibitors of Naja mocambique mocambique phospholipase A(2) with the K-i values of 11, 4, and 15 muM, respectively. With the angle of 1201 between two C(benzene)-O bonds, 1,3-benzene-di-N-octylcarbamate mimics the preferable eclipsed C(sn-2)-O/C(sn-3)-O conformer of phospholipid in the enzyme-phospholipid complex. Further, a three-step phospholipase A(2) inhibition mechanism by the inhibitor is proposed. (C) 2003 Elsevier Ltd. All rights reserved.

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收藏

页码：751 / 755

页数：5

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