title: A novel class of AMPA receptor allosteric modulators. Part 1: design, synthesis, and SAR of 3-aryl-4-cyano-5-substituted-heteroaryl-2-carboxylic acid derivatives.
abstract: The synthesis and initial SAR studies of novel, highly potent positive allosteric modulators of AMPA receptors based on 3-(4-tert-butylphenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid (6a) are described. SAR studies at the thioether moiety indicated that substitution at this position was mandatory and better potency was achieved with small groups.
authors.affiliation: Lilly S.A., Avenida de la Industria, 30, 28108 Alcobendas, Madrid, Spain. fernandez_maria-carmen@lilly.com
authors.forename: Maria-Carmen
authors.initials: MC
authors.lastname: Fernandez
authors.forename: Ana
authors.initials: A
authors.lastname: Castaño
authors.forename: Esteban
authors.initials: E
authors.lastname: Dominguez
authors.forename: Ana
authors.initials: A
authors.lastname: Escribano
authors.forename: Delu
authors.initials: D
authors.lastname: Jiang
authors.forename: Alma
authors.initials: A
authors.lastname: Jimenez
authors.forename: Eric
authors.initials: E
authors.lastname: Hong
authors.forename: William J
authors.initials: WJ
authors.lastname: Hornback
authors.forename: Eric S
authors.initials: ES
authors.lastname: Nisenbaum
authors.forename: Nancy
authors.initials: N
authors.lastname: Rankl
authors.forename: Eric
authors.initials: E
authors.lastname: Tromiczak
authors.forename: Grant
authors.initials: G
authors.lastname: Vaught
authors.forename: Hamideh
authors.initials: H
authors.lastname: Zarrinmayeh
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Zimmerman
mesh_terms: D000494:Allosteric Regulation; D002264:Carboxylic Acids; D015195:Drug Design; D018683:Excitatory Amino Acid Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D018091:Receptors, AMPA / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013440:Sulfides
chemical_list: D002264:Carboxylic Acids; D018683:Excitatory Amino Acid Agents; D006571:Heterocyclic Compounds; D018091:Receptors, AMPA; D013440:Sulfides