Discovery, Synthesis, and Pharmacological Evaluation of Spiropiperidine Hydroxamic Acid Based Derivatives as Structurally Novel Histone Deacetylase (HDAC) Inhibitors

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• 作者：Mario Varasi ; Florian Thaler ; Agnese Abate ; Chiara Bigogno ; Roberto Boggio ; Giacomo Carenzi ; Tiziana Cataudella ; Roberto Dal Zuffo ; Maria Carmela Fulco ; Marco Giulio Rozio ; Antonello Mai ; Giulio Dondio ; Saverio Minucci ; Ciro Mercurio
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：April 28, 2011
• 年：2011
• 卷：54
• 期：8
• 页码：3051-3064
• 全文大小：1174K
• 年卷期：v.54,no.8(April 28, 2011)
• ISSN：1520-4804

文摘

New spiro[chromane-2,4鈥?piperidine] and spiro[benzofuran-2,4鈥?piperidine] hydroxamic acid derivatives as HDAC inhibitors have been identified by combining privileged structures with a hydroxamic acid moiety as zinc binding group. The compounds were evaluated for their ability to inhibit nuclear extract HDACs and for their in vitro antiproliferative activity on different tumor cell lines. This work resulted in the discovery of spirocycle 30d that shows good oral bioavailability and tumor growth inhibition in an HCT-116 murine xenograft model.