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发现3-芳基-5-芳基-1,2,4-恶二唑作为一类新的细胞凋亡诱导剂。2. 鉴定更具水溶性的类似物作为潜在的抗癌药物。

Discovery of 3-aryl-5-aryl-1,2,4-oxadiazoles as a new series of apoptosis inducers. 2. Identification of more aqueous soluble analogs as potential anticancer agents.

作者信息

Kemnitzer William, Kuemmerle Jared, Zhang Han-Zhong, Kasibhatla Shailaja, Tseng Ben, Drewe John, Cai Sui Xiong

机构信息

EpiCept Corporation, Inc. 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.

出版信息

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4410-5. doi: 10.1016/j.bmcl.2009.05.052. Epub 2009 May 18.

DOI:10.1016/j.bmcl.2009.05.052
PMID:19500976
Abstract

As a continuation of our efforts to discover and develop the 3-aryl-5-aryl-1,2,4-oxadiazole series of apoptosis inducers as potential anticancer agents, we explored substitutions at the 2- and 3-positions of the 3-aryl group to improve the aqueous solubility properties and identify development candidates. A small substitution such as methyl or hydroxymethyl at the 2-position was well tolerated. This modification, in combination with a 3-substituted furan ring as the 5-aryl group, resulted in 4g and 4h, which have improved solubility properties. Compound 4g was found to have good in vivo efficacy in animal studies via intravenous administration.

摘要

作为我们发现和开发3-芳基-5-芳基-1,2,4-恶二唑系列凋亡诱导剂作为潜在抗癌药物努力的延续，我们探索了3-芳基的2-位和3-位的取代基，以改善水溶性并确定可供开发的候选物。2-位的小取代基如甲基或羟甲基具有良好的耐受性。这种修饰与作为5-芳基的3-取代呋喃环相结合，得到了4g和4h，它们具有改善的溶解性。在动物研究中发现化合物4g通过静脉给药具有良好的体内疗效。

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