Document Report Card

ID: ALA1139881

Journal: J Med Chem

Title: A tetrazolyl-substituted subtype-selective AMPA receptor agonist.

Authors: Vogensen SB, Frydenvang K, Greenwood JR, Postorino G, Nielsen B, Pickering DS, Ebert B, Bølcho U, Egebjerg J, Gajhede M, Kastrup JS, Johansen TN, Clausen RP, Krogsgaard-Larsen P.

Abstract: 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 AMPA receptor agonist, compound 7, capable of discriminating GluR2-4 from GluR1 by its more than 10-fold preference for the former receptor subtypes. An X-ray crystallographic analysis of this new analogue in complex with the GluR2-S1S2J construct shows that accommodation of the benzyl group creates a previously unobserved pocket in the receptor, which may explain the remarkable pharmacological profile of compound 7.

CiteXplore: 17455929

DOI: 10.1021/jm061439q