title: Synthesis and activity of N-cyanoguanidine-piperazine P2X7 antagonists.
abstract: A novel series of cyanoguanidine-piperazine P2X(7) antagonists were identified and structure-activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X(7) receptors in addition to their ability to inhibit IL-1 beta release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 microM) in this latter assay and demonstrates moderate clearance in-vivo.
authors.affiliation: Abbott Bioresearch Center, Department of Medicinal Chemistry, 381 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Betschmann
authors.forename: Brian
authors.initials: B
authors.lastname: Bettencourt
authors.forename: Diana
authors.initials: D
authors.lastname: Donnelly-Roberts
authors.forename: Michael
authors.initials: M
authors.lastname: Friedman
authors.forename: Jonathan
authors.initials: J
authors.lastname: George
authors.forename: Gavin
authors.initials: G
authors.lastname: Hirst
authors.forename: Nathan
authors.initials: N
authors.lastname: Josephsohn
authors.forename: Donald
authors.initials: D
authors.lastname: Konopacki
authors.forename: Biqin
authors.initials: B
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Maull
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morytko
authors.forename: Nigel Stjohn
authors.initials: NS
authors.lastname: Moore
authors.forename: Marian
authors.initials: M
authors.lastname: Namovic
authors.forename: Paul
authors.initials: P
authors.lastname: Rafferty
authors.forename: Jose-Andres
authors.initials: JA
authors.lastname: Salmeron-Garcia
authors.forename: Edit
authors.initials: E
authors.lastname: Tarcsa
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Kevin
authors.initials: K
authors.lastname: Woller
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006146:Guanidines / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D008956:Models, Chemical; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000737:chemistry; D058486:Receptors, Purinergic P2X7; D013329:Structure-Activity Relationship
chemical_list: D006146:Guanidines; D053583:Interleukin-1beta; C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; D010879:Piperazines; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000077489:Piperazine; C004711:dicyandiamido