title: Synthesis of 24,24-Difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 Derivatives and Evaluation of Their Vitamin D Receptor-Binding Affinity.
abstract: 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.
authors.affiliation: Faculty of Advanced Science and Engineering, Waseda University.
authors.forename: Tanima
authors.initials: T
authors.lastname: Biswas
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Akagi
authors.forename: Kosuke
authors.initials: K
authors.lastname: Usuda
authors.forename: Koji
authors.initials: K
authors.lastname: Yasui
authors.forename: Isao
authors.initials: I
authors.lastname: Shimizu
authors.forename: Mayumi
authors.initials: M
authors.lastname: Okamoto
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
authors.forename: Seijiro
authors.initials: S
authors.lastname: Hosokawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagasawa
mesh_terms: D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*
chemical_list: D018167:Receptors, Calcitriol; D002762:Cholecalciferol