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

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

Volume: 8 Issue: 1

Author(s): Yosuke Demizu, Aki Nakatsu, Yukiko Sato, Shinobu Honzawa, Atsushi Yamashita, Takayuki Sugiura, Atsushi Kittaka, Shigeaki Kato, Haruhiro Okuda and Masaaki Kurihara

Affiliation:

Keywords: Asymmetric reduction, vitamin D receptor, mutant vitamin D receptor, non-secosteroidal ligand, transcriptional assay, molecular modeling study

Abstract: 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.

Cite this article as:

Demizu Yosuke, Nakatsu Aki, Sato Yukiko, Honzawa Shinobu, Yamashita Atsushi, Sugiura Takayuki, Kittaka Atsushi, Kato Shigeaki, Okuda Haruhiro and Kurihara Masaaki, Facile Synthesis of Stereoisomers of the Non-Secosteroidal Ligand LG190178 and their Evaluation Using the Mutant Vitamin D Receptor, Letters in Organic Chemistry 2011; 8 (1) . https://dx.doi.org/10.2174/157017811794557804