2018 Fiscal Year Final Research Report
Development of novel dihydropyrimidine retinoids for medicinal chemistry and drug dicovery
| Project/Area Number |
16K08335
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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 | Yasuda Women's University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
菊地 秀与 城西大学, 薬学部, 助教 (60614055)
久保 貴紀 安田女子大学, 薬学部, 講師 (90435751)
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| Research Collaborator |
Cho Hidetsura
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | ジヒドロピリミジン / レチノイド / タミバロテン / レチノイン酸 / ベキサロテン / RAR / RXR |
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| Outline of Final Research Achievements |
Novel dihydropyrimidines (DPs) exhibiting biological activity inducing differentiation and apoptosis of HL-60 cells were discovered. The activities of the DPs are comparable to those of available agents for acute promyelocytic leukemia, all-trans retinoic acid (ATRA) and tamibarotene. Because the structures of the DPs are quite different from those of ATRA and tamibarotene, and the DPs are novel retinoids and lead compounds for retinoid-based medicinal chemistry and drug dicovery.
Experimental and theoretical studies on the thermodynamics and properties of 2-substituted DPs were undertaken by NMR measurements and DFT calculations. A method of convergent synthesis of novel 4,6-unsubstituted 5-acyl-2-amino DPs using Weinreb amides was also developed.
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| Free Research Field |
有機合成化学、創薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
レチノイドとは、レチノイン酸と類似の活性を有する化合物の総称であり、急性白血病などの治療に用いられている。レチノイドとして機能する既存の低分子医薬品は、レチノイン酸を元にしており、その化学構造が類似している。今回、ジヒドロピリミジンというレチノイン酸と大きく異なる化学構造を有する化合物がレチノイドとして十分に機能することを見出した。ジヒドロピリミジンを基盤とする新たな創薬研究が進展すれば、強力な活性を持ちながら副作用を軽減した医薬品開発につながるだろう。
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