Synthesis and biological evaluation of new 6-s-cis locked 1,2,25-trihydroxyprevitamin D₃ analogues

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• 作者：Laura Sá ; nchez-Abella ; Susana Ferná ; ndez ; Annemieke Verstuyf ; Lieve Verlinden ; Miguel Ferrero ; Vicente Gotor
• 关键词：Vitamin D₃ analogues ; Previtamin D₃ ; Novel A-ring analogues ; Biological evaluation ; Calcitriol
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2007
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 June 2007
• 卷：15
• 期：12
• 页码：4193-4202
• 文件大小：266 K

摘要

An efficient synthesis of several diastereomers of 2-hydroxy substituted 1α,25-dihydroxyprevitamin D₃ derivatives was accomplished utilizing a practical route to the A-ring synthon. The biological activity of the analogues was evaluated in vitro. All the synthesized derivatives demonstrated low affinity for the vitamin D receptor and vitamin D-binding protein compared with 1α,25-dihydroxyvitamin D₃, the natural hormone. 1α,2β,25-trihydroxy-19-nor-pre-D₃ was the most potent of the analogues in inhibiting proliferation of MCF-7 cells but requires higher EC₅₀ concentrations than 1α,25-dihydroxyvitamin D₃.