| Project/Area Number |
25460155
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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 | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
AOYAMA Hiroshi 東京薬科大学, 薬学部, 准教授 (40374699)
KABOUDIN Babak Institute of Advanced Studies in Basic Sciences, Professor
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ホスホン酸 / ホスフィン酸 / 生物活性 / バイオイソスター / 酵素選択性 / 阻害形式 / 結合定数 / 光学分割 / ミミック / プロテアーゼ阻害剤 / トリアゾキノリン類 / 錯体形成 / ジペプチド / ホスホプロリン / ジペプチドイソスター / プロリン / 脱炭酸 / ホスホニル化反応 / プロテアーゼ |
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| Outline of Final Research Achievements |
Phosphonyl and phosphinyl functionalities have been utilized as phosphate mimetics and a bioisostre of carboxylic acids to discover biologically active compounds. In this project, several methods for synthesis of novel phosphonate and phosphinate derivertives have been developed.
A novel series of phosphonate esters was synthesized on the basis of our previously developed aryl carboxylate-type tryptase selective inhibitor. The potency of these synthesized compounds was assessed with an enzyme inhibition assay using three available serine proteases. The phosphonate derivative showed potent thrombin inhibitory activity, whereas it exhibited no or only weak tryptase and trypsin inhibition. The inhibition pattern against thrombin with developed compound is non-competitive in spite of the fact that the lead carboxylate compound is competitive inhibitor.
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