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 language | English (US) |
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Pages (from-to) | 5509-5518 |
Number of pages | 10 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 15 |
Issue number | 16 |
DOIs | |
State | Published - 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