Rational design of a novel AMPA receptor modulator through a hybridization approach

Caldwell, Nicola and Harms, Jonathan E. and Partin, Kathryn M. and Jamieson, Craig (2015) Rational design of a novel AMPA receptor modulator through a hybridization approach. ACS Medicinal Chemistry Letters.

[img] PDF (Caldwell-etal-ACSMCL-2015-Rational-design-of-a-novel-AMPA-receptor-modulator)
Caldwell_etal_ACSMCL_2015_Rational_design_of_a_novel_AMPA_receptor_modulator.pdf
Accepted Author Manuscript

Download (445kB)

    Abstract

    The α-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic 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.