title: Novel and potent 3-(2,3-dichlorophenyl)-4-(benzyl)-4H-1,2,4-triazole P2X7 antagonists.
abstract: Structure-activity relationship (SAR) studies were conducted around early tetrazole-based leads 3 and 4. Replacements for the tetrazole core were investigated and the pendant benzyl substitution was reoptimized with a triazole isostere. Triazole-based P2X(7) antagonists were identified with similar potency to the lead compound 4 but with improved physiochemical properties. Compound 12 was active in a rat model of neuropathic pain.
authors.affiliation: Abbott Laboratories, Neuroscience Research, 100 Abbott Park Road, Abbott Park, IL 60064, USA. william.a.carroll@abbott.com
authors.forename: William A
authors.initials: WA
authors.lastname: Carroll
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Kalvin
authors.forename: Arturo
authors.initials: A
authors.lastname: Perez Medrano
authors.forename: Alan S
authors.initials: AS
authors.lastname: Florjancic
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Diana L
authors.initials: DL
authors.lastname: Donnelly-Roberts
authors.forename: Marian T
authors.initials: MT
authors.lastname: Namovic
authors.forename: George
authors.initials: G
authors.lastname: Grayson
authors.forename: Prisca
authors.initials: P
authors.lastname: Honoré
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
mesh_terms: D000818:Animals; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D058486:Receptors, Purinergic P2X7; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D014230:Triazoles