title: Rational Design of a Novel AMPA Receptor Modulator through a Hybridization Approach.
abstract: The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a family of glutamate ion channels of considerable interest in excitatory neurotransmission and associated disease processes. Here, we demonstrate how exploitation of the available X-ray crystal structure of the receptor ligand binding domain enabled the development of a new class of AMPA receptor positive allosteric modulators (7) through hybridization of known ligands (5 and 6), leading to a novel chemotype with promising pharmacological properties.
authors.affiliation: Department of Pure and Applied Chemistry, University of Strathclyde , 295 Cathedral Street, Glasgow G1 1XL, U.K.
authors.forename: Nicola
authors.initials: N
authors.lastname: Caldwell
authors.affiliation: Department of Biomedical Sciences, Colorado State University , Fort Collins, Colorado 80523-1617, United States.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Harms
authors.affiliation: Department of Biomedical Sciences, Colorado State University , Fort Collins, Colorado 80523-1617, United States.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Partin
authors.affiliation: Department of Pure and Applied Chemistry, University of Strathclyde , 295 Cathedral Street, Glasgow G1 1XL, U.K.
authors.forename: Craig
authors.initials: C
authors.lastname: Jamieson
keywords: AMPA receptor; electrophysiology; hybridization; structure-based drug design