2. Endothelin antagonists: Evaluation of 2,1,3-benzothiadiazole as a methylendioxyphenyl bioisoster

被引：21

作者：

Mederski, WWKR ^{[1
]}

Osswald, M ^{[1
]}

Dorsch, D ^{[1
]}

Anzali, S ^{[1
]}

Christadler, M ^{[1
]}

Schmitges, CJ ^{[1
]}

Wilm, C ^{[1
]}

机构：

[1] Merck KGaA, Preclin Pharmaceut Res, D-64271 Darmstadt, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 01期

关键词：

D O I：

10.1016/S0960-894X(97)10151-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The methylendioxyphenyl group is present in a number of endothelin receptor antagonists thus far reported. By means of a Kohonen neural network we discovered with a benzothiadiazole a bioisosteric replacement instead. This group should be devoid of the negative metabolic interactions with cytochrome P450 ascribed to methylendioxyphenyl in vivo. The synthesis of a potent benzothiadiazole analogue EMD 122801 together with in vitro studies of different methylendioxyphenyl, benzothiadiazole and benzofurazan derivatives is described. (C) 1997 Elsevier Science Ltd. All rights reserved.

引用

页码：17 / 22

页数：6

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