Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
Special Collection of Papers: Regular Articles
Structure–Activity Relationship Study of 3-Amino-2-indolyllactam Derivatives: Development of Inhibitors of Oxidative Stress-Induced Necrosis
Kosuke DodoKenji HayamizuTadashi ShimizuMikiko Sodeoka
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2016 Volume 64 Issue 7 Pages 886-898

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Abstract

Modification of our previously reported selective inhibitor of oxidative stress-induced necrosis, 2-(1H-indol-3-yl)-3-pentylamino-maleimide (IM-54) by regioselective reduction of the C-4 carbonyl group afforded a 3-amino-2-indolyllactam (IL-1) with more potent activity. To examine the structure–activity relationship of IL derivatives, we developed new synthetic routes with flexibility to incorporate a range of substituents at a late stage. The synthesized IL derivatives were evaluated for activity to inhibit necrotic cell death induced by hydrogen peroxide. Among them, IL-12 showed the most potent activity (IC50=49 nM) among the IL and indolylmaleimide (IM) derivatives examined.

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© 2016 The Pharmaceutical Society of Japan
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