Highly antiproliferative, low-calcemic, side-chain ketone analogs of the hormone 1α,25-dihydroxyvitamin D 3

A series 2a– 4b of seven new side-chain ketone analogs of calcitriol ( 1) have been prepared. Unexpectedly, several of these 24- and 25- tert-butyl ketones, even though lacking the classical side-chain tertiary hydroxyl group, are considerably more antiproliferative in vitro than the hormone calcitr...

Full description

Saved in:
Bibliographic Details
Published inBioorganic & medicinal chemistry Vol. 13; no. 19; pp. 5569 - 5580
Main Authors Posner, Gary H., Kim, Hyung Jin, Kahraman, Mehmet, Jeon, Heung Bae, Suh, Byung Chul, Li, Hongbin, Dolan, Patrick, Kensler, Thomas W.
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 01.10.2005
Subjects
Antiproliferative
Calcitriol
Vitamin D
Antiproliferative
Vitamin D
Calcitriol
Online AccessGet full text

Cover

More Information
Summary:A series 2a– 4b of seven new side-chain ketone analogs of calcitriol ( 1) have been prepared. Unexpectedly, several of these 24- and 25- tert-butyl ketones, even though lacking the classical side-chain tertiary hydroxyl group, are considerably more antiproliferative in vitro than the hormone calcitriol ( 1) even at physiologically relevant low nanomolar concentrations and are less calcemic than calcitriol ( 1) in vivo. In addition, ketone analog 19-nor- 2a is not significantly less calcemic in vivo than 19-methylene analog 2a.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2005.06.031