Study and development of a 14-epi-tachysterol skeleton and enhancing bone formation via flexibility of ligand binding domain of vitamin D receptor

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Teikyo University
• Principal Investigator: KITTAKA Atsushi 帝京大学, 薬学部, 教授 (00214833)
• Co-Investigator(Kenkyū-buntansha): TAKANO Masashi 帝京大学, 薬学部, 助教 (50386611)
• Co-Investigator(Renkei-kenkyūsha): SAWADA Daisuke 帝京大学, 薬学部, 准教授 (00338691) ; SUGIYAMA Toru 東京大学, 大学院総合文化研究科, 助教 (40242036) ; SAKAKI Toshiyuki 富山県立大学, 工学部, 教授 (70293909)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬学 / 有機化学 / 合成化学 / ビタミンD / 骨粗鬆症治療薬 / タキステロール / 生物活性 / ビタミンD受容体

Outline of Final Research Achievements

Vitamin D biosynthesis undergoes in human skin with sunshine, and tachysterol is produced as one of the byproducts during the process. Tachysterol is a chemically unstable compound, and it is difficult to study its property. In this project, we synthesized stable tachysterol analogs and clarified their binding mode for human vitamin D receptor (hVDR) by X-ray analysis, and we planned to create desirable osteoporosis chemotherapy. We found that the 19-methyl group is unnecessary for better binding with hVDR, and functionalization of active vitamin D3, which strengthen biological activity, was not suitable for the tachysterol analogs. Although stable tachysterol analogs with a diene system were also synthesized, we found it was not effective on biological activity.

Free Research Field

有機合成化学