title: A novel series of positive modulators of the AMPA receptor: discovery and structure based hit-to-lead studies.
abstract: Starting from an HTS derived hit 1, application of biostructural data facilitated rapid optimization to lead 22, a novel AMPA receptor modulator. This is the first demonstration of how structure based drug design can be exploited in an optimization program for a glutamate receptor.
authors.affiliation: Merck Research Laboratories, MSD, Motherwell, Lanarkshire ML1 5SH, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Jamieson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Basten
authors.forename: Robert A
authors.initials: RA
authors.lastname: Campbell
authors.forename: Iain A
authors.initials: IA
authors.lastname: Cumming
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Gillen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gillespie
authors.forename: Bert
authors.initials: B
authors.lastname: Kazemier
authors.forename: Michael
authors.initials: M
authors.lastname: Kiczun
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lamont
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Lyons
authors.forename: John K F
authors.initials: JK
authors.lastname: Maclean
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Moir
authors.forename: John A
authors.initials: JA
authors.lastname: Morrow
authors.forename: Marianthi
authors.initials: M
authors.lastname: Papakosta
authors.forename: Zoran
authors.initials: Z
authors.lastname: Rankovic
authors.forename: Lynn
authors.initials: L
authors.lastname: Smith
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008861:Microsomes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry* / Q000378:metabolism; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D007191:Indazoles; D018091:Receptors, AMPA; D013876:Thiophenes