Synthesis and characterization of novel seco-steroid analogues bearing small cyclic ethers instead of the hydroxy groups
| Project/Area Number |
16K08337
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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 | Tokushima Bunri University |
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Principal Investigator |
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ステロイド / ホルモン / ビタミン / 化学合成 / 複素環 / 核内受容体 |
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| Outline of Final Research Achievements |
The hormonally active form of seco-steroids, 1alpha,25-dihydroxyvitamin D3, exhibits a broad range of biological activities, in addition to its classical role in calcium homeostasis. Major molecular target of vitamin D is considered to be vitamin D receptor (VDR), which belongs to the nuclear receptor super-family. Insight into the structure-function relationships of the seco-steroids is needed to answer how the subtype-free VDR could deliver a variety of actions. A convergent synthetic method using palladium catalysis allowed us to reach the novel 9,10-seco-steroids bearing small ether structure instead of the hydroxy groups in the A-ring. Preliminary biological evaluation of the novel analogues using bovine thymus VDR suggested that the incorporation of a spiro-oxetane at the C1 position had a beneficial effect on the VDR affinity in comparison with the C3 position counterparts.
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| Academic Significance and Societal Importance of the Research Achievements |
骨強化ホルモンとしてはたらくビタミンDの受容体結合には３つのヒドロキシ基（-OH）が重要な役割を果たしている．しかしながら，ヒドロキシ基には立体化学が存在すること，その近傍が代謝を受けやすいことなどから，同じ役割を果たしながら新しい骨格を有する酸素官能基の開発が求められていた．そこで，新たにエーテル（-O-）構造を有する小さい環をヒドロキシ基の代替とする新しい誘導体を設計した．それらの合成法を確立し，小員環エーテルが水素結合受容体としてはたらくことを見いだした．持続性の高い誘導体への発展が期待できる．
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Report
(5 results)
Research Products
(21 results)
