雌甾-1,3,5(10),6,8-五烯-2,16α-二醇的合成与发现。
Synthesis and Discovery of Estra-1,3,5(10),6,8-pentaene-2,16α-diol.
机构信息
Department of Chemistry, Burke Laboratory , Dartmouth College , Hanover , New Hampshire 03756 , United States.
Geisel School of Medicine , Dartmouth College , Lebanon , New Hampshire 03755 , United States.
出版信息
Org Lett. 2018 Oct 5;20(19):6220-6224. doi: 10.1021/acs.orglett.8b02689. Epub 2018 Sep 17.
A metallacycle-centered approach to the assembly of partially aromatic synthetic steroids was investigated as a means to prepare a boutique collection of unique steroidal agents. The synthesis and discovery of estra-1,3,5(10),6,8-pentaene-2,16α-diol (VII) is described, along with structure-activity relationships related to its cytotoxic properties. Overall, VII was found to have a GI = 0.2 μg/mL (∼800 nM) in MDA-MB-231 human breast cancer cells, be an efficacious estrogen receptor agonist with potency for ERβ > ERα (ERβ EC = 21 nM), possess selective affinity to the cdc-2-like kinase CLK4 (K = 350 nM), and be phenotypically related to paclitaxel by an unbiased panel assessment.
研究了一种基于金属环的方法来组装部分芳香合成甾体，以制备独特甾体药物的精品系列。本文描述了estra-1,3,5(10),6,8-戊烯-2,16α-二醇（VII）的合成和发现，以及与其细胞毒性性质相关的结构-活性关系。总体而言，VII 在 MDA-MB-231 人乳腺癌细胞中的 GI = 0.2 μg/mL（约 800 nM），是一种有效的雌激素受体激动剂，对 ERβ>ERα（ERβ EC = 21 nM）具有效力，对 cdc-2 样激酶 CLK4 具有选择性亲和力（K = 350 nM），并通过无偏面板评估与紫杉醇表现出相关关系。
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