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Improved synthesis and in vitro/in vivo activities of natural product-inspired, artificial glutamate analogs

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/43115

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)

Submitter: 酒井 隆一

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