Antiproliferative, low-calcemic, fluorinated sulfone analogs of 1α,25-dihydroxyvitamin D3: Chemical synthesis and biological evaluation

Aimee R. Usera, Patrick M. Dolan, Thomas W. Kensler, Gary H. Posner

Research output: Contribution to journalArticlepeer-review

Abstract

Novel fluorinated sulfone analogs of the hormone 1α,25-dihydroxyvitamin D3 have been designed and synthesized in order to study the biological effects of fluorine incorporation at the terminus of the C,D-ring side chain. Although biologically active 26,27-hexafluorinated 1α,25-dihydroxyvitamin D3 analogs have been synthesized previously, this investigation reports the first successful fluorinated series in which trifluoromethyl sulfone analogs present a favorable biological profile. This study shows that two new analogs featuring incorporation of a synthetically simple single trifluoromethyl sulfone group have significantly increased antiproliferative activity while causing desirably low in vivo calciuria relative to that of calcitriol. Incorporation of additional fluorines, as in a perfluorobutyl analog, results in a loss of antiproliferative activity.

Original languageEnglish (US)
Pages (from-to)5509-5518
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number16
DOIs
StatePublished - Aug 15 2007

Keywords

  • Calcitriol
  • Fluorinated sulfones
  • Trifluoromethyl
  • Vitamin D

ASJC Scopus subject areas

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

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