| Project/Area Number |
15K08031
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ビタミンD / 合成化学 / 生理活性 / 有機化学 / 薬学 / ビタミンＤ |
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| Outline of Final Research Achievements |
The synthesis of (24R)-2alpha-[2-(tetrazol-2-yl)ethyl]-1alpha,24,25-trihydroxyvitamin D3, which is the major metabolite of 2 alpha -[2-(tetrazol-2-yl)ethyl]-1alpha,25-dihydroxyvitamin D3 (AH-1) by CYP24A1, has been achieved. Convergent syntheses of novel 19-norvitamin D analogs with a azole at the C2 position possessing the alkyl linker have been achieved. These syntheses are characterized as useful syntheses with the high efficiency and yield, so that other ligands would be synthesized in these synthetic ways. Binding affinity for vitamin D receptor (VDR) of these ligands, transactivation activity of osteocalcin promoter in HOS cells, and metabolism by CYP24A1 have been also studied.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題の成果として得られた2位置換ビタミンD誘導体の代謝過程の解明は、CYP24A1に対して抵抗性のあるリガンドを獲得し、ビタミンD誘導体によるCYP24A1選択的な阻害剤の開発研究に大きく貢献するものである。確立した合成ルートは、引き続き他のヘテロ環や、アルキル鎖長を有するA環部位の合成へと展開し、さらに新しい誘導体合成につなげることが可能であるため、医薬品リード化合物獲得を目的とする今後のリガンドデザインに大きく寄与するものである。
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