Investigation of discovery of seed compound utilizing the change of conformation by the modification of inactive structural moiety

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22725
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Tokyo University of Science
• Principal Investigator: Murata Takatsugu 東京理科大学, 理学部第一部応用化学科, 助教 (80883355)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: M-COPA / 創薬研究 / コンフォメーション

Outline of Final Research Achievements

The modified compound, which was structurally changed from the standard compound without alterations of structural moiety related its bioactivity, was synthesized. It was expected that this alteration affected conformational change and made the bioactivity drastically improving. As a result, the biological activity was significantly changed, and it was indicated that the modification of the structural moiety not related to bioactivity changed the conformation of the structural skeleton.
As above, this research presented the method of drug discovery that utilizes the conformational change caused by alteration of the structural change not related to the bioactivity.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

創薬研究は主に平面性の高い分子構造を持つ化合物を対象に行われてきたが、近年は三次元性に富んだ構造を持つ化合物が着目されるようになってきた。しかしながら、分子構造を変化させることでコンフォメーションの変化、すなわち三次元的構造の変化を生み、その変化を利用する創薬研究はほとんど行われてこなかった。本研究は非活性部位の改質によりコンフォメーション変化が薬理活性に大きな影響を及ぼすことを明らかにしており、創薬研究における学術的意義があると言える。