The Rhodadyns, a New Class of Small Molecule Inhibitors of Dynamin GTPase Activity

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• 作者：Mark J. Robertson ; Gordana Hadzic ; Joseph Ambrus ; D. Yuri Pom猫 ; Emily Hyde ; Ainslie Whiting ; Anna Mariana ; Lisa von Kleist ; Ngoc Chau ; Volker Haucke ; Phillip J. Robinson ; Adam McCluskey
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：May 10, 2012
• 年：2012
• 卷：3
• 期：5
• 页码：352-356
• 全文大小：328K
• 年卷期：v.3,no.5(May 10, 2012)
• ISSN：1948-5875

文摘

Six focused rhodanine-based libraries, 60 compounds in total, were synthesized and evaluated as potential dynamin I GTPase inhibitors. Twenty-six were more potent than the lead compound with 13 returning IC₅₀ values 鈮?0 渭M, making the Rhodadyn series among the most active dynamin inhibitors reported. Two analogues were highly effective at blocking receptor-mediated endocytosis: C10 and D10 with IC_50(RME) = 7.0 卤 2.2 and 5.9 卤 1.0 渭M, respectively. These compounds are equipotent with the best reported in-cell dynamin inhibitors.

Keywords:

dynamin inhibition; Knoevengal condensation; rhodanine