title: Synthesis and in vitro activity of N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide P2X7 antagonists.
abstract: A novel series of cyanoguanidine-piperazine P2X(7) antagonists was designed based upon the structure of A-740003. Structure-activity relationship (SAR) studies focused on the piperazine moiety and the right hand side substitution. Compounds were assayed for activity at human and rat P2X(7) receptors and compound 29 was found to possess potent activity (IC(50)=30-60 nM) at both species.
authors.affiliation: Abbott Bioresearch Center, Department of Medicinal Chemistry, 381 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morytko
authors.forename: Patrick
authors.initials: P
authors.lastname: Betschmann
authors.forename: Kevin
authors.initials: K
authors.lastname: Woller
authors.forename: Anna
authors.initials: A
authors.lastname: Ericsson
authors.forename: Haipeng
authors.initials: H
authors.lastname: Chen
authors.forename: Diana L
authors.initials: DL
authors.lastname: Donnelly-Roberts
authors.forename: Marian T
authors.initials: MT
authors.lastname: Namovic
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: William A
authors.initials: WA
authors.lastname: Carroll
authors.forename: Paul
authors.initials: P
authors.lastname: Rafferty
mesh_terms: D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C529337:N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide; C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; D010879:Piperazines; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins