Conformationally restricted mimics of vitamin D rotamers.
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.
Okamura
W H
WH
Department of Chemistry, University of California, Riverside 92521, USA. william.okamura@ucr.edu
Do
S
S
Kim
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Jeganathan
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Vu
T
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Zhu
G D
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Norman
A W
AW
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D018716:Molecular Mimicry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002117:Calcitriol