（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.
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。
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