Design, synthesis, and biological activity of D-bishomo-1 α,25-dihydroxyvitamin D < sub > 3 < /sub > analogs and their crystal structures with the vitamin D nuclear receptor

In this study, we present the synthesis of vitamin D derivatives characterized by an enlarged (seven-membered) ring D. Preparation of the designed vitamin D compounds required separate syntheses of crucial building blocks (C/D-rings fragments with side chain and rings A) which were combined by different methods, including Wittig-Horner reaction and Suzuki coupling. Biological activities of the target vitamin D analogs were assessed both in vitro and in vivo, demonstrating their significant potency compared to the natural hormone. Furthermore, the successful crystallization of these compounds with the vitamin D receptor (VDR) enabled us to investigate additional molecular interactions with this protein.PMID:38615411 | DOI:10.1016/j.ejmech.2024.116403
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research