Document Report Card

ID: ALA1144430

Journal: J Med Chem

Title: Convergent synthesis and pharmacology of substituted tetrazolyl-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid analogues.

Authors: Vogensen SB, Clausen RP, Greenwood JR, Johansen TN, Pickering DS, Nielsen B, Ebert B, Krogsgaard-Larsen P.

Abstract: The synthesis and pharmacological characterization of 1- and 2-alkyltetrazolyl analogues of (RS)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA), a highly potent and selective agonist at AMPA receptors, are presented. A shorter and more convergent synthetic route than previously described, employing a new method for introducing the amino acid moiety, was developed for these derivatives. The 2-substituted isomers were selective agonists, and their activity correlated inversely with the size of the substituent. Structural explanations of the structure-activity relationship are provided.

CiteXplore: 15857151

DOI: 10.1021/jm050014l