Q4 · MEDICINE
Article
Author: Zarrinmayeh, Hamideh ; Hornback, William J. ; Fernandez, Carmen ; Castano, Ana ; Zimmerman, Dennis M. ; Jimenez, Alma ; Escribano, Ana ; Ho, Ken H. ; Tromiczak, Eric ; Rankl, Nancy ; Dominguez, Esteban ; Nisenbaum, Eric S.
The synthesis and structure-activity relationship (SAR) of novel and highly potent positive allosteric modulators of AMPA receptors, 3-biphenyl-4-yl-4-cyano-5-ethyl-1-methyl-1H-pyrrole-2-carboxylic acid, are described. These studies indicated that higher potency was achieved with ortho substitution of the distal (D) phenyl of the 3-biphenyl ring and resulted in the discovery of a potent pyrrole LY2059346 (23q), that was selected for further evaluation in in vitro native tissue assays and in vivo experiments.