Facile Synthesis of Stereoisomers of the Non-Secosteroidal Ligand LG190178 and their Evaluation Using the Mutant Vitamin D Receptor

We developed a facile synthesis process for producing optically active non-secosteroidal ligands (YR301-304), which are stereoisomers of LG190178, and evaluated their performance in transcriptional assays using mutant vitamin D receptor (VDR). It was found that all of them had stronger activities than the natural ligand 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3]. In particular, YR301 showed potent activity for both wild-type and mutant Arg274Leu VDR.