Elucidation of axial chirality in sulfonamide and development of novel medicinal compounds
| Project/Area Number |
16K08326
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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 | Teikyo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
夏苅 英昭 新潟薬科大学, 薬学部, 客員研究員 (00334334)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 軸不斉 / スルホンアミド / スルホンアミド構造 / 軸性キラリティー |
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| Outline of Final Research Achievements |
The 5N-arylsulfonyl-1,5-benzodiazepin-2-ones with antiproliferative activity were prepared and successfully separated into the (aR)- and (aS)-atropisomers with extraordinary stability (ΔG‡= ∼130 kJ/mol) by freezing the conformation around the sp2－sp2 axis in an Ar－N(SO2) moiety with a C6-methyl group. Also, by introducing a C3-methyl group (central chirality) into the 1,5-benzodiazepine nucleus, the stereochemistry at the axis was biased to take solely one diastereomer with a relative stereochemistry of (aS*,3S*). The (aS) stereochemistry and the folded form of the molecule were revealed to be important for exerting the antiproliferative activity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において、キラリティーの存在が認識されていないスルホンアミド構造をキラリティーの観点から追究・解明し、生物活性との相関を明らかにしたことは、従来の中心不斉に着目した創薬研究に限らず、軸不斉を意識した新たな創薬研究の重要性を周知させるものとなった。スルホンアミド構造を有する医薬品はたいへん多く、スルホンアミドのキラリティーの解明が医薬品の分子設計を変えることに繋がり、より有用性の高い医薬品開発を通じて社会へ大きく貢献するものである。また、中心不斉から始まったキラリティーの概念をより幅広く広げる役割も担っており医薬化学分野だけでなく、基礎的な有機化学分野への波及効果も高いと言える。
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Report
(5 results)
Research Products
(25 results)
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[Journal Article] Atropisomeric and Conformational Properties of 6N-Benzoyl- and 6N-p-Tosyl-1,6-benzodiazocines: Comparison with Those of 1,5-Benzodiazepines2019
Author(s)
Tabata, Hidetsugu; Murai, Kazuya: Funaki, Kaoru; Takemae, Chihiro; Tasaka, Tomohiko; Oshitari, Tetsuta; Takahashi, Hideyo; Natsugari, Hideaki.
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Journal Title
Heterocycles
Volume: 99
Issue: 1
Pages: 566-566
DOI
Related Report
Peer Reviewed
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[Journal Article] Atropisomerism in the 2,3,4,5-Tetrahydro-1H-1,5-benzodiazepine Nucleus: Effects of Central Chirality at C3 on the N-Mesylation Reaction2018
Author(s)
Tabata, Hidetsugu; Tsuji, Yuka; Yoneda, Tetsuya; Tasaka, Tomohiko; Oshitari, Tetsuta; Takahashi, Hideyo; Natsugari, Hideaki
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Journal Title
Synlett
Volume: 29
Issue: 16
Pages: 2141-2146
DOI
Related Report
Peer Reviewed
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