title: Discovery of potent and selective adamantane-based small-molecule P2X(7) receptor antagonists/interleukin-1beta inhibitors.
abstract: A novel series of antagonists of the human P2X7 receptor is described. Modification of substituents enabled identification of compounds selective for the rat P2X7 receptor and provides useful pharmacological tools for evaluation of the role of P2X7 in disease.
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leics, U.K. mark1.furber@astrazeneca.com
authors.forename: Mark
authors.initials: M
authors.lastname: Furber
authors.forename: Lilian
authors.initials: L
authors.lastname: Alcaraz
authors.forename: Janice E
authors.initials: JE
authors.lastname: Bent
authors.forename: Armin
authors.initials: A
authors.lastname: Beyerbach
authors.forename: Keith
authors.initials: K
authors.lastname: Bowers
authors.forename: Martin
authors.initials: M
authors.lastname: Braddock
authors.forename: Moya V
authors.initials: MV
authors.lastname: Caffrey
authors.forename: David
authors.initials: D
authors.lastname: Cladingboel
authors.forename: John
authors.initials: J
authors.lastname: Collington
authors.forename: David K
authors.initials: DK
authors.lastname: Donald
authors.forename: Malbinder
authors.initials: M
authors.lastname: Fagura
authors.forename: Frank
authors.initials: F
authors.lastname: Ince
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Kinchin
authors.forename: Celine
authors.initials: C
authors.lastname: Laurent
authors.forename: Mandy
authors.initials: M
authors.lastname: Lawson
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Luker
authors.forename: Michael M P
authors.initials: MM
authors.lastname: Mortimore
authors.forename: Austen D
authors.initials: AD
authors.lastname: Pimm
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Riley
authors.forename: Nicola
authors.initials: N
authors.lastname: Roberts
authors.forename: Mark
authors.initials: M
authors.lastname: Robertson
authors.forename: Jill
authors.initials: J
authors.lastname: Theaker
authors.forename: Philip V
authors.initials: PV
authors.lastname: Thorne
authors.forename: Richard
authors.initials: R
authors.lastname: Weaver
authors.forename: Peter
authors.initials: P
authors.lastname: Webborn
authors.forename: Paul
authors.initials: P
authors.lastname: Willis
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D009000:Monocytes / Q000378:metabolism; D011485:Protein Binding; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D058486:Receptors, Purinergic P2X7; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D001798:Blood Proteins; D053583:Interleukin-1beta; C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D000218:Adamantane