Conformationally restricted mimics of vitamin D rotamers

Steroids. 2001 Mar-May;66(3-5):239-47. doi: 10.1016/s0039-128x(00)00147-1.

Abstract

Drug developments in the vitamin D field have continued to focus on structure-function studies of analogs produced by chemically modifying the structure of 1alpha,25-dihydroxyvitamin D(3) (1,25-D3) and its metabolites. Direct structural information gleaned from X-ray crystallographic or NMR studies regarding the ligand-receptor complex and other guest-host systems, which are likely involved in initiating biologic responses, also offers potential insight into drug design. Evidence has accrued suggesting that topologically different conformers of 1,25-D3 may bind to proteins in different ways, including the induction of different conformations of protein. This paper concerns our progress on the chemical synthesis of analogs (e.g. ansa-steroids, suprasterols, vinylallenes and other analogs) conformationally locked or at least rotationally restricted to mimic higher energy conformers of 1,25-D3.

Publication types

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

MeSH terms

  • Animals
  • Calcitriol / analogs & derivatives
  • Calcitriol / chemistry*
  • Humans
  • Molecular Conformation
  • Molecular Mimicry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Calcitriol