Synthesis and structure-activity relationship of p-carborane-based non-secosteroidal vitamin D analogs

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• 作者：Shinya Fujii ; Atsushi Kano ; Chalermkiat Songkram ; Hiroyuki Masuno ; Yoshiyuki Taoda ; Emiko Kawachi ; Tomoya Hirano ; Aya Tanatani ; Hiroyuki Kagechika
• 关键词：Vitamin D ; Nuclear receptor ; Carborane ; Non-secosteroid
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：15 February, 2014
• 年：2014
• 卷：22
• 期：4
• 页码：1227-1235
• 全文大小：840 K

文摘

1伪,25-Dihydroxyvitamin D₃ [1伪,25(OH)₂D₃: 1] is a specific modulator of nuclear vitamin D receptor (VDR), and novel vitamin D analogs are therapeutic candidates for multiple clinical applications. We recently developed non-secosteroidal VDR agonists bearing a p-carborane cage (a carbon-containing boron cluster) as a hydrophobic core structure. These carborane derivatives are structurally quite different from classical secosteroidal vitamin D analogs. Here, we report systematic synthesis and activity evaluation of carborane-based non-secosteroidal vitamin D analogs. The structure-activity relationships of carborane derivatives are different from those of secosteroidal vitamin D derivatives, and in particular, the length and the substituent position of the dihydroxylated side chain are rather flexible in carborane derivatives. The structure-activity relationships presented here should be helpful in development of non-secosteroidal vitamin D analogs for clinical applications.