Portal de Periódicos da CAPES

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

2014; Elsevier BV; Volume: 22; Issue: 4 Linguagem: Inglês

10.1016/j.bmc.2014.01.015

1464-3391

Shinya Fujii, Atsushi Kano, Chalermkiat Songkram, Hiroyuki Masuno, Yoshiyuki Taoda, Emiko Kawachi, Tomoya Hirano, Aya Tanatani, Hiroyuki Kagechika,

Pharmacological Effects and Toxicity Studies

1α,25-Dihydroxyvitamin D3 [1α,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.