title: New P2X3 receptor antagonists. Part 2: Identification and SAR of quinazolinones.
abstract: Numerous potent P2X3 antagonists have been discovered and the therapeutic potential of P2X3 antagonism already comprises proof-of-concept data obtained in clinical trials with the most advanced compound. We have lately reported the discovery and optimization of thia-triaza-tricycle compounds with potent P2X3 antagonistic properties. This Letter describes the SAR of a back-up series containing a 4-oxo-quinazoline central ring. The discovery of the highly potent compounds 51 is presented.
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szántó
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Makó
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Vágó
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Hergert
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Bata
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Farkas
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Kolok
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Mónika
authors.initials: M
authors.lastname: Vastag
mesh_terms: D042462:4-Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D011485:Protein Binding; D058920:Purinergic P2X Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D052999:Quinazolinones / Q000737:chemistry* / Q000378:metabolism; D058477:Receptors, Purinergic P2X3 / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D042462:4-Quinolones; D058920:Purinergic P2X Receptor Antagonists; D052999:Quinazolinones; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate
keywords: 4-Oxo-6-aryl-phenethyl-quinazolines; ATP; Chronic cough; Ion channel; Nanomolar activity; P2X3 antagonist; Purinergic receptor; Structure–activity relationship