1998 Fiscal Year Final Research Report Summary
SYNTHESIS OF PYRROLIDINONE DERIVATIVES ORIENTED TO THE FUNCTION OF THE BRAIN
| Project/Area Number |
09672288
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCE |
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Principal Investigator |
NAGASAKA Tatsuo TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCE,SCHOOL OF PHARMACY,PROFESSOR, 薬学部, 教授 (90057331)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Hiroto TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCE,SCHOOL OF PHARMACY,ASSISTANT, 薬学部, 助手 (50246675)
KOSUGI Yoshiyuki TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCE,SCHOOL OF PHARMACY,INSTRUCTER, 薬学部, 講師 (00120147)
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| Project Period (FY) |
1997 – 1998
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| Keywords | FUNCTION OF BRAIN / DEMENTIA / ANIRACETAM / LACTAM / PYROGLUTAMIC ACID / PASSIVE AVOIDANCE / ACTIVE AVOIDANCE / TILIVALLINE |
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| Research Abstract |
For the development of drugs, 2-pyrrolidinone derivatives were synthesized from L-pyro-glutamic acid. These derivatives were designed based on aniracetam, a drug for senile dementia, and kainoids possessing activities in the central nervous system. Many reactions of(2R,5S)-2-aryl-1-aza-3-oxabicyclo[3.3.0]oct-6-ene-8-one with sulfoxyranes, 1,3-dipolars and Michael donors and the following hydrolysis of the products were examined. Stereoselective and regioselective products were obtained in good yields by these reactions.
In the passive and active aviodance responses in mice, several compounds were found to have strong effects than those of aniracetam, so this skeleton, (2R,5S)-2-aryl-1-aza-3-oxabicyclo-[3.3.0]octan-8-one, was expected to be a new type lead compound for the senile dementia.
Synthesis of tilivalline, a natural product having a lactam in the molecule, was accomplished for the pharmacological test.
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