| Project/Area Number |
23590141
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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 | Kobe Pharmaceutical University |
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Principal Investigator |
WADA Akimori 神戸薬科大学, 薬学部, 教授 (80158683)
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| Co-Investigator(Renkei-kenkyūsha) |
OKANO Toshio 神戸薬科大学, 薬学部, 教授 (20131542)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 9cis-レチノイン酸 / ヘテロダイマー / クロスカップリング / テルペン誘導体 / ビニルトリフラート / スズオレフィン / RXR / 9cis-レチノイン酸アナログ |
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| Research Abstract |
Retinoid X receptor (RXR) agonists are interesting candidates for the treatment of metabolic syndrome. 9-Cis-retinoic acid (9cRA) is a natural RXR agonist, that also works as a retinoic acid receptor (RAR) agonist. In the study of the structure-activity relationship of RXR agonists, we prepared the analogs, in which the cyclohexene ring of 9cRA is replaced with bulkier hydrophobic moieties.
As the first candidates, the analogs having various cyclic terpenoid moieties were synthesized and evaluated their RXR and RAR agonistic activities. The results of transcriptional assay showed that the compound (MentViMe), which possess a menthane skeleton, exhibited RXR-selective agonistic activity. In next, the analogs a menthone-benzene fused bicyclic system as the lipophilic domain (MentPhMe and MentPhEt) were synthesized. The methyl congener (MentPhMe) showed PPARgamma/RXRalpha-agonistic activity, on the other side, the ethyl congener (MentPhEt) showed LXRalpha/RXRalpha-agonistic activity.
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