Substituted indoles as potent and orally active 5-lipoxygenase activating protein (FLAP) inhibitors

被引：12

作者：

Frenette, R

Hutchinson, JH

Léger, S

Thérien, M

Brideau, C

Chan, CC

Charleson, S

Ethier, D

Guay, J

Jones, TR

McAuliffe, M

Piechuta, H

Riendeau, D

Tagari, P

Girard, Y

机构：

[1] Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

[2] Merck & Co Inc, W Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 16期

关键词：

D O I：

10.1016/S0960-894X(99)00399-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This paper reports on the SAR investigation of inhibitors of 5-lipoxygenase activating protein (FLAP) based on MK-0591. Emphasis was made on modifications to the nature of the link between the indole and the quinoline moieties, to the substitution pattern around the two heterocycles and to possible replacements of the quinoline moiety. Lead optimization culminated in (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(pyridin-2-ylmethoxy)-indol-2-yl]-2,2-dimethylpropanoic acid (18k), as a potent inhibitor of leukotriene biosynthesis that is well absorbed and active in functional models. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：2391 / 2396

页数：6

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