Comprehensive Synthesis of Side-Chain Fluorinated 2α-[2-(Tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 Analogs and Preliminary Biological Activities

Chemical and Pharmaceutical Bulletin 2026 Open access

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Authors: Fumihiro Kawagoe, Sayuri Mototani, Yuki Okamoto, Souma Murata, Akiko Takeuchi, Tomofumi Yatsu, Kaori Yasuda, Yusuke Akagi, Toshie Fujishima, Yoshiki Miyata, Hiroshi Saitoh, Toshiyuki Sakaki
+1 more Atsushi Kittaka
DOI: 10.1248/cpb.c25-00710
Cited by: 2
References: 29

Abstract

Twelve side-chain fluorinated 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D 3 (AH-1) analogs were designed, synthesized, and evaluated regarding their biological activities.Synthesis was carried out employing the palladium-catalyzed Trost coupling reaction between side-chain fluorinated CD-ring bromo-olefins 41-52 and A-ring enyne 53.Some analogs, including C26,27-hexafluoro-AH-1 (31) and 24,24-difluoro-AH-1 (34), exhibited much higher human vitamin D receptor binding affinity, VDR-ligand binding domain transcriptional activity, osteocalcin promoter transactivation activity, and metabolic resistance to CYP24A1mediated inactivation than 1α,25(OH) 2 D 3 .

Fields of Study & Subjects

Click Chemistry and Applications Synthesis of Tetrazole Derivatives Synthesis and Reactivity of Heterocycles

Publication details

Journal / source
Chemical and Pharmaceutical Bulletin
Publisher
Pharmaceutical Society of Japan
Volume
74
Issue
1
Pages
103–118
Publication date
29 January 2026
Language
EN