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抗增殖性4-(1,2,4-恶二唑-5-基)哌啶-1-甲酰胺，一种新型微管蛋白抑制剂化学类型。

Antiproliferative 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides, a new tubulin inhibitor chemotype.

作者信息

Krasavin Mikhail, Sosnov Andrey V, Karapetian Ruben, Konstantinov Igor, Soldatkina Olga, Godovykh Elena, Zubkov Fedor, Bai Ruoli, Hamel Ernest, Gakh Andrei A

机构信息

Department of Chemistry, St. Petersburg State University, Peterhof 198504, Russia.

ORCHIMED, Institute of Physiologically Active Compounds, Chernogolovka, Moscow Region 142432, Russia.

出版信息

Bioorg Med Chem Lett. 2014 Sep 15;24(18):4477-4481. doi: 10.1016/j.bmcl.2014.07.089. Epub 2014 Aug 8.

DOI:10.1016/j.bmcl.2014.07.089
PMID:25155551
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4191898/
Abstract

We discovered a new chemical class of antiproliferative agents, 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides. SAR-guided optimization of the two distinct terminal fragments yielded a compound with 120 nM potency in an antiproliferative assay. Biological activity profile studies (COMPARE analysis) demonstrated that 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides act as tubulin inhibitors, and this conclusion was confirmed via biochemical assays with pure tubulin and demonstration of increased numbers of mitotic cells following treatment of a leukemia cell line.

摘要

我们发现了一类新的抗增殖剂，即4-(1,2,4-恶二唑-5-基)哌啶-1-甲酰胺。通过对两个不同末端片段进行SAR导向的优化，得到了一种在抗增殖试验中活性为120 nM的化合物。生物活性谱研究（COMPARE分析）表明，4-(1,2,4-恶二唑-5-基)哌啶-1-甲酰胺可作为微管蛋白抑制剂，这一结论通过对纯微管蛋白的生化试验以及对白血病细胞系处理后有丝分裂细胞数量增加的证明得到了证实。

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