Highly antiproliferative, low-calcemic, side-chain ketone analogs of the hormone 1alpha,25-dihydroxyvitamin D3.
Highly antiproliferative, low-calcemic, side-chain ketone analogs of the hormone 1alpha,25-dihydroxyvitamin D3.
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激素 1α,25-二羟基维生素 D3 的高度抗增殖、低钙血症侧链酮类似物。
DOI：
10.1016/j.bmc.2005.06.031
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Kensler,ThomasW
中科院分区：
文献类型：
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作者：
Posner,GaryH;Kim,HyungJin;Kahraman,Mehmet;Jeon,HeungBae;Suh,ByungChul;Li,Hongbin;Dolan,Patrick;Kensler,ThomasW
合成了骨化三醇（1）的7个新的侧链酮类似物（2a-4 b）。出乎意料的是，这些24-和25-叔丁基酮中的几种，即使缺乏经典的侧链叔羟基，即使在生理学相关的低纳摩尔浓度下，在体外也比激素骨化三醇（1）具有显著更强的抗增殖性，并且在体内比骨化三醇（1）具有更少的钙离子。此外，酮类似物19-nor-2a在体内的钙代谢并不显著低于19-亚甲基类似物2a。
A series 2a–4b of seven new side-chain ketone analogs of calcitriol (1) have been prepared. Unexpectedly, several of these 24- and 25-tert-butyl ketones, even though lacking the classical side-chain tertiary hydroxyl group, are considerably more antiproliferative in vitro than the hormone calcitriol (1) even at physiologically relevant low nanomolar concentrations and are less calcemic than calcitriol (1) in vivo. In addition, ketone analog 19-nor-2a is not significantly less calcemic in vivo than 19-methylene analog 2a.