Design, Synthesis, and Cytoprotective Effect of 2-Aminothiazole Analogues as Potent Poly(ADP-Ribose) Polymerase-1 Inhibitors

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• 作者：Wen-Ting Zhang ; Jin-Lan Ruan ; Peng-Fei Wu ; Feng-Chao Jiang ; Li− ; Na Zhang ; Wei Fang ; Xiang-Long Chen ; Yue Wang ; Bao-Shuai Cao ; Gang-Ying Chen ; Yi-Jing Zhu ; Jun Gu ; Jian-Guo Chen
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：February 12, 2009
• 年：2009
• 卷：52
• 期：3
• 页码：718-725
• 全文大小：277K
• 年卷期：v.52,no.3(February 12, 2009)
• ISSN：1520-4804

文摘

A series of novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors were designed within 2-aminothiazole analogues (4−10) based on a constructed three-dimensional pharmacophore model. After synthesis, the inhibitory effect on PARP-1 activity and the cytoprotective action of these compounds were tested and evaluated. Among them, compounds 4−6 and 10 appeared to be potent PARP-1 inhibitors with IC₅₀ values less than 1 μM, which had been perfectly predicted by pharmacophore model. These compounds proved to be highly potent against cell injury induced by H₂O₂ and oxygen-glucose deprivation (OGD) in PC12 cells. These novel 2-aminothiazole analogues are potentially applicable as neuroprotective agents for the treatment of neurological diseases.