Synthesis and biological activities of vitamin D3 derivatives with cyanoalkyl side chain at C-2 position

Hiroshi Saitoh; Hidekazu Watanabe; Shinji Kakuda; Midori Takimoto-Kamimura; Kenichiro Takagi; Akiko Takeuchi; Kazuya Takenouchi

doi:10.1016/j.jsbmb.2014.12.004

Synthesis and biological activities of vitamin D3 derivatives with cyanoalkyl side chain at C-2 position

J Steroid Biochem Mol Biol. 2015 Apr:148:27-30. doi: 10.1016/j.jsbmb.2014.12.004. Epub 2014 Dec 10.

Authors

Hiroshi Saitoh¹, Hidekazu Watanabe², Shinji Kakuda², Midori Takimoto-Kamimura², Kenichiro Takagi², Akiko Takeuchi², Kazuya Takenouchi²

Affiliations

¹ Teijin Institute for Bio-Medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan. Electronic address: [email protected].
² Teijin Institute for Bio-Medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan.

PMID: 25500068
DOI: 10.1016/j.jsbmb.2014.12.004

Abstract

We synthesized and evaluated novel vitamin D3 derivatives with cyanoalkyl side chain at C-2 position on the basis of our previous research for 2α side chain which bears nitrogen atom-containing functional group. Through a study of X-ray co-crystal structures of human VDR and compound 3, we demonstrated that the 2α alkyl side chain in compound 3 shows a novel interaction in the complex of hVDR-LBD and ligand. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

Keywords: 2α-Functionalized vitamin D; Binding affinity; Transactivation; Vitamin D receptor; Vitamin D(3); X-ray co-crystallographic analysis.

Publication types

Review

MeSH terms

Alkanes / chemistry*
Calcitriol / analogs & derivatives*
Calcitriol / chemical synthesis
Calcitriol / pharmacology*
Drug Design
Humans
Molecular Structure
Nitrogen / chemistry*
Structure-Activity Relationship
Vitamins / chemical synthesis*
Vitamins / pharmacology*

Substances

Alkanes
Vitamins
Calcitriol
Nitrogen