Small-molecular inhibitors of Ca2+-induced mitochondrial permeability transition (MPT) derived from muscle relaxant dantrolene
Small-molecular inhibitors of Ca2+-induced mitochondrial permeability transition (MPT) derived from muscle relaxant dantrolene
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DOI：
10.1016/j.bmc.2012.08.062
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发表时间：
2012-11-01
影响因子：
3.5
通讯作者：
Aoyama, Hiroshi
中科院分区：
文献类型：
--
作者：
Murasawa, Shinpei;Iuchi, Katsuya;Aoyama, Hiroshi
由通过酰胺键与5-（卤代苯基）呋喃-2-基连接的取代的乙内酰脲组成的结构被鉴定为用于开发治疗血管功能障碍（包括缺血/再灌注损伤）的低分子量治疗剂的有前景的支架。在所合成的化合物中，5-（3，5-二氯苯基）-N-{2，4-二氧代-3-[（吡啶-3-基）甲基]咪唑烷-1-基}-2-呋喃酰胺（17）对Ca ~（2+）诱导的线粒体肿胀具有最强的抑制活性。介绍了这些化合物的结构发展、合成及其构效关系。(C)2012爱思唯尔有限公司保留所有权利。
A structure consisting of substituted hydantoin linked to a 5-(halophenyl)furan-2-yl group via an amide bond was identified as a promising scaffold for development of low-molecular-weight therapeutic agents to treat vascular dysfunction, including ischemia/reperfusion injury. Among the compounds synthesized, 5-(3,5-dichlorophenyl)-N-{2,4-dioxo-3-[(pyridin-3-yl)methyl]imidazolidin-1-yl}-2-furamide (17) possessed the most potent inhibitory activity against Ca2+-induced mitochondrial swelling. The structural development, synthesis and structure-activity relationship of these compounds are described. (C) 2012 Elsevier Ltd. All rights reserved.