title: A novel class of positive allosteric modulators of AMPA receptors: design, synthesis, and structure-activity relationships of 3-biphenyl-4-yl-4-cyano-5-ethyl-1-methyl-1H-pyrrole-2-carboxylic acid, LY2059346.
abstract: 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.
authors.affiliation: Eli Lilly and Co, Lilly Research Laboratories, Indianapolis, IN 46285, USA. Zarrinmayeh_Hamideh@lilly.com
authors.forename: Hamideh
authors.initials: H
authors.lastname: Zarrinmayeh
authors.forename: Eric
authors.initials: E
authors.lastname: Tromiczak
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Zimmerman
authors.forename: Nancy
authors.initials: N
authors.lastname: Rankl
authors.forename: Ken H
authors.initials: KH
authors.lastname: Ho
authors.forename: Esteban
authors.initials: E
authors.lastname: Dominguez
authors.forename: Ana
authors.initials: A
authors.lastname: Castaño
authors.forename: Ana
authors.initials: A
authors.lastname: Escribano
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernandez
authors.forename: Alma
authors.initials: A
authors.lastname: Jimenez
authors.forename: William J
authors.initials: WJ
authors.lastname: Hornback
authors.forename: Eric S
authors.initials: ES
authors.lastname: Nisenbaum
mesh_terms: D000494:Allosteric Regulation; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D018846:Excitatory Amino Acids / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000819:agonists*; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D002264:Carboxylic Acids; D018846:Excitatory Amino Acids; D011758:Pyrroles; D018091:Receptors, AMPA; D018698:Glutamic Acid