Novel 1alpha,25-dihydroxyvitamin D3 analogues with the side chain at C12

Journal of Medicinal Chemistry
Xosé C González-AviónDino Moras

Abstract

The plethora of actions of 1alpha,25(OH)2D3 in various systems suggested wide clinical applications of vitamin D nuclear receptor (VDR) ligands in treatments of inflammation, dermatological indication, osteoporosis, cancers, and autoimmune diseases. More than 3000 vitamin D analogues have been synthesized in order to reduce the calcemic side effects while maintaining the transactivation potency of the natural ligand. In light of the crystal structures of the vitamin D nuclear receptor (VDR), novel analogues of the hormone 1alpha,25(OH)2D3 with side chains attached to C-12 were synthesized via the convergent Wittig-Horner approach. Among the compounds studied, the analogue 2b showed the highest binding affinity for VDR and was the most potent at inducing VDR transcriptional activity in a transient transfection assay (20% of the transactivation activity of the natural ligand).

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Citations

Mar 30, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Silvina Eduardo-CanosaAntonio Mouriño
Oct 27, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Diego M CarballaMercedes Torneiro
Mar 28, 2012·Expert Opinion on Therapeutic Patents·Carsten CarlbergAntonio Mouriño
Oct 8, 2016·Organic & Biomolecular Chemistry·Hovsep Stambulyan, Thomas G Minehan
Aug 24, 2020·European Journal of Medicinal Chemistry·Jingxuan ChenJianjun Chen
Jun 8, 2021·Chemical Science·Benjamin D A ShennanDarren J Dixon
Apr 29, 2011·Journal of Medicinal Chemistry·Maria A RegueiraMercedes Torneiro
Jun 9, 2020·Journal of Medicinal Chemistry·Izabela K Sibilska-KaminskiHector F DeLuca
Jun 26, 2018·Journal of Medicinal Chemistry·Mami YoshizawaKeiko Yamamoto

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