当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Indole cytosolic phospholipase A2 alpha inhibitors: discovery and in vitro and in vivo characterization of 4-{3-[5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1-(diphenylmethyl)-1H-indol-3-yl]propyl}benzoic acid, efipladib.

Indole cytosolic phospholipase A2 alpha inhibitors: discovery and in vitro and in vivo characterization of 4-{3-[5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1-(diphenylmethyl)-1H-indol-3-yl]propyl}benzoic acid, efipladib.

Abstract：

:The optimization of a class of indole cPLA 2 alpha inhibitors is described herein. The importance of the substituent at C3 and the substitution pattern of the phenylmethane sulfonamide region are highlighted. Optimization of these regions led to the discovery of 111 (efipladib) and 121 (WAY-196025), which are shown to be potent, selective inhibitors of cPLA 2 alpha in a variety of isolated enzyme assays, cell based assays, and rat and human whole blood assays. The binding of these compounds has been further examined using isothermal titration calorimetry. Finally, these compounds have shown efficacy when dosed orally in multiple acute and chronic prostaglandin and leukotriene dependent in vivo models.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

McKew JC,Lee KL,Shen MW,Thakker P,Foley MA,Behnke ML,Hu B,Sum FW,Tam S,Hu Y,Chen L,Kirincich SJ,Michalak R,Thomason J,Ipek M,Wu K,Wooder L,Ramarao MK,Murphy EA,Goodwin DG,Albert L,Xu X,Donahue F,Ku MS,Keit

doi

10.1021/jm701467e

subject

Has Abstract

pub_date

2008-06-26 00:00:00

pages

3388-413

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

51

pub_type

杂志文章

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