The secosteroidal hormone 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is a specific ligand of nuclear vitamin D receptor (VDR), and novel vitamin D analogs are promising candidates for multiple clinical applications. We previously developed a series of 1,12-dicarba-closo-dodecaborane (p-carborane) derivatives as nonsecosteroidal VDR agonists. Here, we report the synthesis and structure-activity relationship of p-carborane-based nonsecosteroidal vitamin D analogs bearing a nitrogen or a sulfur atom in the linker structure. Biological evaluation revealed that the structure–activity relationships of amine derivatives and sulfide derivatives are different, and therefore the choice of the linker structure significantly affects the activity. We also found that benzylamine structure could be a lead scaffold for novel vitamin D analogs. The structure–activity relationships presented here should be helpful in further development of nonsecosteroidal vitamin D analogs.

中文翻译：

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1,12-二氨基甲杂-十二烷基硼烷类三醇衍生物作为非甾体类维生素D类似物的合成及构效关系研究

甾类固醇激素1α，25-二羟含氧维生素D 3 [1α，25（OH）2 D 3 ]是核维生素D受体（VDR）的特定配体，新型维生素D类似物有望用于多种临床应用。我们以前开发了一系列1,12- dicarba-的闭合碳-dodecaborane（p -carborane）衍生物nonsecosteroidal VDR激动剂。在这里，我们报道了p的合成和构效关系-在连接结构中带有氮或硫原子的基于碳氢化合物的非甾体类维生素D类似物。生物学评估表明，胺衍生物和硫化物衍生物的结构-活性关系不同，因此接头结构的选择会显着影响活性。我们还发现苄胺结构可能是新型维生素D类似物的铅骨架。此处介绍的结构活性关系应有助于进一步发展非甾体类维生素D类似物。