3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3

被引：19

作者：

Havran, Lisa M. ^{[1
]}

Chong, Dan C. ^{[1
]}

Childers, Wayne E. ^{[1
]}

Dollings, Paul J. ^{[1
]}

Dietrich, Arlene ^{[1
]}

Harrison, Boyd L. ^{[1
]}

Marathias, Vasilios ^{[1
]}

Tawa, Gregory ^{[1
]}

Aulabaugh, Ann ^{[2
]}

Cowling, Rebecca ^{[2
]}

Kapoor, Bhupesh ^{[2
]}

Xu, Weixin ^{[3
]}

Mosyak, Lidia ^{[3
]}

Moy, Franklin ^{[3
]}

Hum, Wah-Tung ^{[3
]}

Wood, Andrew ^{[4
]}

Robichaud, Albert J. ^{[1
]}

机构：

[1] Wyeth Res, Chem Sci, Princeton, NJ 08543 USA

[2] Wyeth Res, Screening Sci, Pearl River, NY 10965 USA

[3] Wyeth Res, Chem Sci, Cambridge, MA 02140 USA

[4] Wyeth Res, Discovery Neurosci, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 22期

关键词：

Caspase-3; Stroke; Apoptosis; Pyrimidoindolone; CELL-DEATH; APOPTOSIS; INJURY; SAR;

D O I：

10.1016/j.bmc.2009.09.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cysteine-dependant aspartyl protease (caspase) activation has been implicated as a part of the signal transduction pathway leading to apoptosis. It has been postulated that caspase-3 inhibition could attenuate cell damage after an ischemic event and thereby providing for a novel neuroprotective treatment for stroke. As part of a program to develop a small molecule inhibitor of caspase-3, a novel series of 3,4-dihydropyrimido(1,2-a)indol-10(2H)-ones (pyrimidoindolones) was identified. The synthesis, biological evaluation and structure-activity relationships of the pyrimidoindolones are described. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：7755 / 7768

页数：14

共 31 条

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