Synthesis and Biological Activities of (R)- and (S)-N-(4-Methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium Chloride as Potent Cytotoxic Antitubulin Agents

被引：18

作者：

Ganglee, Aleem ^{[1
]}

Zhao, Ying ^{[1
]}

Hamel, Ernest ^{[2
]}

Westbrook, Cara ^{[3
]}

Mooberry, Susan L. ^{[3
]}

机构：

[1] Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, Pittsburgh, PA 15282 USA

[2] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA

[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 17期

基金：

美国国家卫生研究院;

关键词：

III BETA-TUBULIN; COLCHICINE SITE; CANCER; OVEREXPRESSION; CONFIGURATION; RESISTANCE; DISCOVERY; ANALOGS;

D O I：

10.1021/jm2007722

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(R,S)-1 is a potent antimitotic compound. (R)-1 center dot HCl and (S)-1 center dot HCl were synthesized from (R)- and (S)-3-methyladipic acid. Both enantiomers were potent inhibitors of cell proliferation and caused cellular microtubule loss and mitotic arrest. They inhibited purified tubulin assembly and the binding of [H-3]colchicine to tubulin, with (S)-1 being about twice as potent. Cytotoxicity against 60 tumor cell lines, however, indicated that the (S)-isomer was 10- to 88-fold more potent than the (R)-isomer.

引用

页码：6151 / 6155

页数：5

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