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Improved synthesis and in vitro/in vivo activities of natural product-inspired, artificial glutamate analogs
Title: | Improved synthesis and in vitro/in vivo activities of natural product-inspired, artificial glutamate analogs |
Authors: | Oikawa, Masato Browse this author | Ikoma, Minoru Browse this author | Sasaki, Makoto Browse this author | Gill, Martin B. Browse this author | Swanson, Geoffrey T. Browse this author | Shimamoto, Keiko Browse this author | Sakai, Ryuichi Browse this author |
Keywords: | Diversity-oriented synthesis | Glutamate receptor | Hypoactivity | Deoxygenation of amide |
Issue Date: | 1-Jun-2010 |
Publisher: | Elsevier |
Journal Title: | Bioorganic & Medicinal Chemistry |
Volume: | 18 |
Issue: | 11 |
Start Page: | 3795 |
End Page: | 3804 |
Publisher DOI: | 10.1016/j.bmc.2010.04.044 |
Abstract: | Here, we report our second-generation synthesis of 12 artificial glutamate analogs, starting from heterotricycle intermediates 3a-3d, readily prepared in three steps including tandem Ugi/Diels-Alder reactions. The new synthesis employs imidate intermediates for the deoxygenation of pyrrolidones (10a-10d to 6a-6d), and each advanced intermediate 6a-6d was diversified into three glutamate analogs (1a-1d, 5a-5d, 7a-7d) in 1-2 steps. In vitro electrophysiological assays revealed that the new piperidine-type analog 7c alters neuronal function with lower potency than 1a. Conversely, intracranial injection of 7c into mice produced a greater degree of hypoactivity than 1a. Our recent investigation has revealed that this series of compounds antagonizes AMPA-type glutamate receptor-mediated currents in a subtype selective manner. The more efficient syntheses of this novel set of neuroactive molecules will facilitate their pharmacological characterization. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/43115 |
Appears in Collections: | 水産科学院・水産科学研究院 (Graduate School of Fisheries Sciences / Faculty of Fisheries Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 酒井 隆一
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