title: Discovery of P2X3 selective antagonists for the treatment of chronic pain.
abstract: Purinergic receptor P2X3 has been linked to analgesia in a number of pre-clinical models of pain, and is expressed in the human pain perception pathway. Only few P2X3-selective antagonists have been reported to date. This Letter describes the SAR and in vivo analgesic profile of a novel scaffold of selective P2X3 antagonists.
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca R&D, 7171 Frederick-Banting, Montréal, QC, Canada H4S 1Z9. Louis-david.cantin@astrazeneca.com
authors.forename: Louis-David
authors.initials: LD
authors.lastname: Cantin
authors.forename: Malken
authors.initials: M
authors.lastname: Bayrakdarian
authors.forename: Christophe
authors.initials: C
authors.lastname: Buon
authors.forename: Eric
authors.initials: E
authors.lastname: Grazzini
authors.forename: Yun-Jin
authors.initials: YJ
authors.lastname: Hu
authors.forename: Jean
authors.initials: J
authors.lastname: Labrecque
authors.forename: Carmen
authors.initials: C
authors.lastname: Leung
authors.forename: Xuehong
authors.initials: X
authors.lastname: Luo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martino
authors.forename: Michel
authors.initials: M
authors.lastname: Paré
authors.forename: Kemal
authors.initials: K
authors.lastname: Payza
authors.forename: Nirvana
authors.initials: N
authors.lastname: Popovic
authors.forename: Denis
authors.initials: D
authors.lastname: Projean
authors.forename: V
authors.initials: V
authors.lastname: Santhakumar
authors.forename: Christopher
authors.initials: C
authors.lastname: Walpole
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Yu
authors.forename: Mirosław J
authors.initials: MJ
authors.lastname: Tomaszewski
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D057166:High-Throughput Screening Assays; D006801:Humans; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D058919:Purinergic P2 Receptor Antagonists / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use; D011744:Pyrimidinones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D058477:Receptors, Purinergic P2X3 / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries
chemical_list: D000700:Analgesics; D058919:Purinergic P2 Receptor Antagonists; D011744:Pyrimidinones; D011758:Pyrroles; D058477:Receptors, Purinergic P2X3; D054852:Small Molecule Libraries