The secosteroidal hormone 1α,25-dihydroxyvitamin D 3 [1α,25(OH) 2 D 3 ] 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.