A Tetrazolyl-Substituted Subtype-Selective AMPA Receptor Agonist

详细信息    查看全文

• 作者：Stine B. Vogensen ; Karla Frydenvang ; Jeremy R. Greenwood ; Giovanna Postorino ; Birgitte Nielsen ; Darryl S. Pickering ; Bjarke Ebert ; Ulrik B//pubs.acs.org/images/gifchars/oslash.gif" bord
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：May 17, 2007
• 年：2007
• 卷：50
• 期：10
• 页码：2408 - 2414
• 全文大小：394K
• 年卷期：v.50,no.10(May 17, 2007)
• ISSN：1520-4804

文摘

Replacement of the methyl group of the AMPA receptor agonist 2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA) with a benzyl group provided the first AMPAreceptor agonist, compound 7, capable of discriminating GluR2-4 from GluR1 by its more than 10-foldpreference for the former receptor subtypes. An X-ray crystallographic analysis of this new analogue incomplex with the GluR2-S1S2J construct shows that accommodation of the benzyl group creates a previouslyunobserved pocket in the receptor, which may explain the remarkable pharmacological profile of compound7.