title: A novel series of positive modulators of the AMPA receptor: structure-based lead optimization.
abstract: Starting from lead compound 1, we demonstrate how X-ray structural data can be used to understand SAR and expediently optimize bioavailability in a novel series of AMPA receptor modulators, furnishing 5 with improved bioavailability and robust in vivo activity.
authors.affiliation: Merck Research Laboratories, MSD, Newhouse, Motherwell, Lanarkshire, UK. craig.jamieson@strath.ac.uk
authors.forename: Craig
authors.initials: C
authors.lastname: Jamieson
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: Frederic
authors.initials: F
authors.lastname: Martin
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Moir
authors.forename: John A
authors.initials: JA
authors.lastname: Morrow
authors.forename: John
authors.initials: J
authors.lastname: Pantling
authors.forename: Zoran
authors.initials: Z
authors.lastname: Rankovic
authors.forename: Lynn
authors.initials: L
authors.lastname: Smith
mesh_terms: D000494:Allosteric Regulation; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D011720:Pyrazoles; D018091:Receptors, AMPA