2016 Fiscal Year Final Research Report
Rational Development of Novel Hemagglutinin-based Influenza Virus Inhibitors
| Project/Area Number |
26460158
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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 | Hoshi University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | インフルエンザ / ヘマグルチニン / ムメフラール / 不斉合成 / キラル分割 / 共結晶 / 構造活性相関 |
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| Outline of Final Research Achievements |
Influenza A virus infects cells by the action of hemagglutinin (HA) and neuraminidase (NA). Mumefural (MF), isolated from Japanese apricot extract, is the first compound which shows inhibitory effect against both HA and NA activities of H1N1 influenza virus (A/Narita/1/2009). For the development of new anti-influenza drugs, total synthesis of (±)-MFwas achieved in 6 steps and 80 derivatives of MF were prepared. Their structure-activity relationship studies have revealed hydroxy dicarboxylic acid moiety was important for expression of the inhibition activity. The derivatives with bulky ester moiety improved the activity. A new compound 10 having adamantane framework on the ester part was synthesized, and its activity was 10 times more potent than that of MF. In addition, a 7-step asymmetric synthesis was developed, and both enantiomers were synthesized starting from (S) and (R)-malic acids. We have confirmed (S)-MF has an inhibitory activity 2 times stronger than that of (R)-MF.
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| Free Research Field |
有機化学
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