Structure activity relationship study of bile acid derivatives to development of novel vitamin D receptor ligand

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MASUNO Hiroyuki 東京医科歯科大学, 生体材料工学研究所, 技術専門職員 (80376714)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ビタミンＤ / 核内受容体 / 胆汁酸 / 構造活性相関

Outline of Final Research Achievements

To develop potent vitamin D receptor ligand which have no vitamin D skeleton and to investigate structure and activity relationships of lithocolic acid derivateves, I designed, synthesized and evaluated biological activity of novel lithocholic acid derivateves. I synthesized several lithocholic acid derivatives which have hydoxyl group containing alkyl group at carbon three on steroid skeleton. The vitamin D receptor activity of synthesized compounds were evaluated by differentiation-inducing activity in HL-60 human promyelocytic leukemia cell line. All of the compounds have higher activity than known lithocholic acid derivatives. The most potent compound have activity as well as 1,25-dihydroxyvitamin D3. These compounds have enough activities to use clinical application.

Free Research Field

有機化学