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本文引用的文献

1
Synthesis and discovery of water-soluble microtubule targeting agents that bind to the colchicine site on tubulin and circumvent Pgp mediated resistance.水溶性微管靶向剂的合成与发现，该靶向剂与微管蛋白上的秋水仙素结合部位结合，并规避 Pgp 介导的耐药性。
J Med Chem. 2010 Nov 25;53(22):8116-28. doi: 10.1021/jm101010n. Epub 2010 Oct 25.
2
Design, synthesis, and biological evaluations of 2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoline analogs of combretastatin-A4.2,5-二芳基-2,3-二氢-1,3,4-噁二唑啉类化合物的设计、合成及构效关系研究。
J Med Chem. 2010 Jan 14;53(1):325-34. doi: 10.1021/jm901268n.
3
The taccalonolides: microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms.他卡缩醇内酯类：一类能规避临床上相关紫杉烷耐药机制的微管稳定剂。
Cancer Res. 2008 Nov 1;68(21):8881-8. doi: 10.1158/0008-5472.CAN-08-2037.
4
Asymmetric synthesis of 2,3-dihydro-2-arylquinazolin-4-ones: methodology and application to a potent fluorescent tubulin inhibitor with anticancer activity.2,3-二氢-2-芳基喹唑啉-4-酮的不对称合成：方法及其在具有抗癌活性的强效荧光微管蛋白抑制剂中的应用
J Med Chem. 2008 Aug 14;51(15):4620-31. doi: 10.1021/jm800271c. Epub 2008 Jul 9.
5
Cytoskeleton and paclitaxel sensitivity in breast cancer: the role of beta-tubulins.细胞骨架与乳腺癌中的紫杉醇敏感性：β-微管蛋白的作用
Int J Cancer. 2007 May 15;120(10):2078-85. doi: 10.1002/ijc.22557.
6
Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients.III类β-微管蛋白过表达是晚期卵巢癌患者临床预后不良的一个标志物。
Clin Cancer Res. 2006 May 1;12(9):2774-9. doi: 10.1158/1078-0432.CCR-05-2715.
7
A common pharmacophore for a diverse set of colchicine site inhibitors using a structure-based approach.使用基于结构的方法确定的多种秋水仙碱位点抑制剂的共同药效团。
J Med Chem. 2005 Sep 22;48(19):6107-16. doi: 10.1021/jm050502t.
8
Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy.Ⅲ类β-微管蛋白的表达可预测接受长春瑞滨化疗的非小细胞肺癌患者的预后。
Clin Cancer Res. 2005 Aug 1;11(15):5481-6. doi: 10.1158/1078-0432.CCR-05-0285.
9
Expression of class III beta tubulin in non-small cell lung cancer is correlated with resistance to taxane chemotherapy.III类β微管蛋白在非小细胞肺癌中的表达与对紫杉烷化疗的耐药性相关。
Bull Cancer. 2005 Feb;92(2):E25-30.
10
Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients.III类β微管蛋白过表达是卵巢癌患者对紫杉醇耐药的一个主要机制。
Clin Cancer Res. 2005 Jan 1;11(1):298-305.

（R）-和（S）-N-（4-甲氧基苯基）-N，2，6-三甲基-6，7-二氢-5H-环戊并[d]嘧啶-4-胺盐酸盐的合成及作为有效细胞毒性抗微管蛋白剂的生物活性。

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.

机构信息

Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, Pennsylvania 15282, USA.

出版信息

J Med Chem. 2011 Sep 8;54(17):6151-5. doi: 10.1021/jm2007722. Epub 2011 Aug 5.

DOI:10.1021/jm2007722
PMID:21786793
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3184787/
Abstract

(R,S)-1 is a potent antimitotic compound. (R)-1·HCl and (S)-1·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 [(3)H]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.

摘要

（R，S）-1 是一种有效的抗有丝分裂化合物。（R）-1·HCl 和（S）-1·HCl 是由（R）-和（S）-3-甲基己二酸合成的。两种对映异构体都是有效的细胞增殖抑制剂，可导致细胞微管丢失和有丝分裂阻滞。它们抑制纯化微管的组装和 [(3)H]秋水仙碱与微管的结合，（S）-1 的活性约为（R）-1 的两倍。然而，对 60 种肿瘤细胞系的细胞毒性表明，（S）-异构体的活性比（R）-异构体强 10 到 88 倍。