Synthesis of 24,24-Difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 Derivatives and Evaluation of Their Vitamin D Receptor-Binding Affinity

Synthesis of 24,24-Difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 Derivatives and Evaluation of Their Vitamin D Receptor-Binding Affinity

Two vitamin D3 derivatives, namely 24,24-difluoro-1β,3β,25-dihydroxy-19-norvitamin D3 (6a) and 24,24-difluoro-1α,3α,25-dihydroxy-19-norvitamin D3 (6b), were synthesized via a convergent route employing Julia–Kocienski olefination as a key step. Compounds 6a and b bound to vitamin D receptor (VDR) wi...

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Veröffentlicht in:Biological & pharmaceutical bulletin 2016/08/01, Vol.39(8), pp.1387-1391
Hauptverfasser: Biswas, Tanima, Akagi, Yusuke, Usuda, Kosuke, Yasui, Koji, Shimizu, Isao, Okamoto, Mayumi, Uesugi, Motonari, Hosokawa, Seijiro, Nagasawa, Kazuo
Format: Artikel
Sprache:eng
Schlagworte:
24,24-difluoro-19-norvitamin D3
Cholecalciferol - analogs & derivatives
Cholecalciferol - metabolism
cis-A ring synthon
Julia–Kocienski coupling
Receptors, Calcitriol - metabolism
vitamin D
vitamin D receptor binding
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Zusammenfassung:Two vitamin D3 derivatives, namely 24,24-difluoro-1β,3β,25-dihydroxy-19-norvitamin D3 (6a) and 24,24-difluoro-1α,3α,25-dihydroxy-19-norvitamin D3 (6b), were synthesized via a convergent route employing Julia–Kocienski olefination as a key step. Compounds 6a and b bound to vitamin D receptor (VDR) with IC50 values of 64.8 and 57.6 nM, respectively, exhibiting about 400- and 30-fold greater binding affinity than the corresponding non-fluorinated derivatives 5a and b.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b16-00316