Synthesis of 2α-heteroarylalkyl active vitamin D3 with therapeutic effect on enhancing bone mineral density in vivo

Miki Matsuo, Asami Hasegawa, Masashi Takano, Hiroshi Saito, Shinji Kakuda, Takayuki Chida, Ken Ichiro Takagi, Eiji Ochiai, Kyohei Horie, Yoshifumi Harada, Midori Takimoto-Kamimura, Kazuya Takenouchi, Daisuke Sawada, Atsushi Kittaka

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


2α-Heteroarylethyl-1α,25-dihydroxyvitamin D3 analogues, which were designed to form a hydrogen bond between Arg274 of human vitamin D receptor (hVDR) and a nitrogen atom of the heteroaromatic ring at the 2α-position, were synthesized. Among them, 2α-[2-(tetrazol-2-yl) ethyl]-1α,25-dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats, osteoporosis model animals, on enhancing bone mineral density than those of active vitamin D 3. X-ray cocrystallographic analysis of the hVDR-ligand complex confirms that the new hydrogen bond formation stabilized the complex.

Original languageEnglish
Pages (from-to)671-674
Number of pages4
JournalACS Medicinal Chemistry Letters
Issue number7
Publication statusPublished - Jul 11 2013
Externally publishedYes


  • Vitamin D
  • X-ray cocrystallographic analysis
  • bone mineral density
  • in vivo antiosteoporotic effect
  • osteocalcin
  • vitamin D receptor

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry


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