title: Thieno[2,3-b]pyridines as negative allosteric modulators of metabotropic GluR5 receptors: hit-to-lead optimization.
abstract: An HTS campaign of our corporate compound library resulted in thieno[2,3-b]pyridines derivative hits with mGluR5 negative allosteric modulator effects. During the hit-to-lead development our objective was to improve affinity, and to keep the ligand efficiency values at an acceptable level. After different modifications of the linker resulted in a 2-sulfonyl-thieno[2,3-b]pyridines derivative, which fulfilled the lead criteria.
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Nógrádi
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary. Electronic address: g.wagner@richter.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Wágner
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Domány
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Amrita
authors.initials: A
authors.lastname: Bobok
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Magdó
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Kiss
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: Katalin
authors.initials: K
authors.lastname: Fónagy
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Háda
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Kóti
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Gál
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Farkas
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: György M
authors.initials: GM
authors.lastname: Keserű
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Greiner
authors.affiliation: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szombathelyi
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D058924:Thienopyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D058924:Thienopyridines
keywords: Negative allosteric modulator; mGluR5