Highly antiproliferative, low-calcemic, side-chain ketone analogs of the hormone 1α,25-dihydroxyvitamin D3

Gary H. Posner, Jin Kim Hyung, Mehmet Kahraman, Bae Jeon Heung, Chul Suh Byung, Hongbin Li, Patrick Dolan, Thomas W. Kensler

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5569-5580
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number19
DOIs
StatePublished - Oct 1 2005

Keywords

  • Antiproliferative
  • Calcitriol
  • Vitamin D

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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