2017 Fiscal Year Final Research Report
Development of Novel Tau Protein-Binding Compounds Based on the Alkene-to-Chloroalkene Isosteric Switch Strategy
| Project/Area Number |
16K15142
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Shizuoka University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | PET薬剤 / タウタンパク質 / 神経原繊維変化 / PBB3 |
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| Outline of Final Research Achievements |
As part of a program aimed at identifying the utility of haloalkene-containing molecules, synthetic and evaluation studies of chloroalkene-conjugated PBB3 derivative, ITY11-397, were performed for the development of novel tau-imaging PET tracers with improved operability. ITY11-397 was designed based on the alkene-to-chloroalkene isosteric switching strategy and can be prepared in 8 steps from 2-chloro-5-cyanopyridine. Evaluation study on the photostability revealed that the photostability of ITY11-397 is 6-fold higher than that of the corresponding unsubstituted compound. In addition, ITY11-397 showed higher binding selectivity to the 2N3R-type Tau protein. The main advantage of such chloroalkene-conjugated systems lies in their simple chemical modification, making possible the application of this strategy to various molecules with acyclic conjugated system(s), which should contribute to the development of photoresistant molecules with conjugated system(s).
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| Free Research Field |
創薬化学、有機合成化学、ペプチド化学
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