2013 Fiscal Year Final Research Report
Development of retinoic acid analog exhibiting a separeted function of the heterodimeric-nuclear receptors
| 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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| 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 |
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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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Research Products
(28 results)
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[Journal Article] Menadione (Vitamin K3) Is a Catabolic Product of Oral Phylloquinone (Vitamin K1) in the Intestine and a Circulating Precursor of Tissue Menaquinone-4 (Vitamin K2) in Rats2013
Author(s)
Y. Hirota, N. Tugawa, K. Nakagawa, Y. Suhara, K. Tanaka, Y. Uchino, A. Takeuchi, N. Sawada, M. Kamao, A. Wada, T. Okitsu, T. Okano
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Journal Title
J. Biol. Chem
Volume: 288
Pages: 33071-33080
DOI
Peer Reviewed
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[Journal Article] Structure-Activity Relationship of Novel Menaquinone-4 Analogues : Modification of the Side Chain Affects their Biological Activities2012
Author(s)
Y. Suhara, N. Honda, T. Okitsu, M. Sakai, M. Watanabe, K. Nakagawa, A. Wada, K. Takeda, K. Takahashi, H. Tokiwa, T. Okano
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Journal Title
J. Med. Chem
Volume: 55
Pages: 1553-1558
DOI
Peer Reviewed
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