Design and synthesis of 1-indol-1-yl-propan-2-ones as inhibitors of human cytosolic phospholipase A2α

被引：70

作者：

Ludwig, J ^{[1
]}

Bovens, S ^{[1
]}

Brauch, C ^{[1
]}

Elfringhoff, AS ^{[1
]}

Lehr, M ^{[1
]}

机构：

[1] Univ Munster, Inst Pharmaceut & Med Chem, D-48149 Munster, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 08期

关键词：

D O I：

10.1021/jm051243a

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and structure-activity relationship study of a series of 1-indol-1-yl-3-phenoxypropan-2-one inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha) are described. The compounds were evaluated in a vesicle assay with isolated cPLA(2)alpha and in cellular assays with intact human platelets. Systematic variation led to 3-methylhydrogen 1-[3-(4-decyloxyphenoxy)-2-oxopropyl]indole-3,5-dicarboxylate (57), which revealed the highest activity against the isolated enzyme. With an IC50 value of 4.3 nM in this assay, it is one of the most potent in vitro cPLA(2)alpha inhibitors known today.

引用

页码：2611 / 2620

页数：10

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