Synthetic studies of (23S,25R)-1α,25-dihydroxyvitamin D3 26,23-lactone (calcitriol lactone) and its derivatives

J Steroid Biochem Mol Biol. 2018 Mar:177:240-246. doi: 10.1016/j.jsbmb.2017.07.017. Epub 2017 Jul 27.

Abstract

(23S,25R)-1α,25-Dihydroxyvitamin D3 26,23-lactone (calcitriol lactone) is a major metabolite of 1α,25-dihydroxyvitamin D3 that binds to vitamin D receptor (VDR) and exhibits various biological activities. This lactone and its derivatives are considered to have potential as drug candidates to treat VDR-related diseases, but their biological activities have not yet been fully characterized, mainly because of their limited availability by chemical synthesis. This review deals with synthetic studies of calcitriol lactone, and its derivatives, i.e., methylene lactones (TEI-9647 and its derivatives) and calcitriol lactams (DLAMs). We also discuss their biological activities, VDR-binding affinity and structure-activity relationships.

Keywords: Antagonist; Calcitriol lactam (DLAM); Calcitriol lactone; Side chain; TEI-9647.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemistry*
  • Calcitriol / pharmacology
  • Humans
  • Lactams / chemistry*
  • Lactams / pharmacology
  • Lactones / chemistry*
  • Lactones / pharmacology
  • Receptors, Calcitriol / metabolism

Substances

  • Lactams
  • Lactones
  • Receptors, Calcitriol
  • VDR protein, human
  • Calcitriol