TY - JOUR
T1 - Synthesis of 24,24-difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 derivatives and evaluation of their vitamin D receptor-binding affinity
AU - Biswas, Tanima
AU - Akagi, Yusuke
AU - Usuda, Kosuke
AU - Yasui, Koji
AU - Shimizu, Isao
AU - Okamoto, Mayumi
AU - Uesugi, Motonari
AU - Hosokawa, Seijiro
AU - Nagasawa, Kazuo
N1 - Publisher Copyright:
© 2016 The Pharmaceutical Society of Japan.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - 24,24-difluoro-19-norvitamin D
KW - Julia-Kocienski coupling
KW - Vitamin D
KW - Vitamin D receptor binding
KW - cis-A ring synthon
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U2 - 10.1248/bpb.b16-00316
DO - 10.1248/bpb.b16-00316
M3 - Article
C2 - 27476947
AN - SCOPUS:84979992185
SN - 0918-6158
VL - 39
SP - 1387
EP - 1391
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 8
ER -