title: Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists.
abstract: Hit-to-lead optimization of a HTS hit led to new carbamoyloxime derivatives. After identification of an advanced hit (8d) the CYP enzyme inhibitory activity of this class of compounds was successfully eliminated. Systematic exploration of different parts of the advanced hit led us to some promising lead compounds with mGluR5 affinities comparable to that of MPEP.
authors.affiliation: Gedeon Richter Plc, Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Galambos
authors.forename: Gábor
authors.initials: G
authors.lastname: Wágner
authors.forename: Katalin
authors.initials: K
authors.lastname: Nógrádi
authors.forename: Attila
authors.initials: A
authors.lastname: Bielik
authors.forename: László
authors.initials: L
authors.lastname: Molnár
authors.forename: Amrita
authors.initials: A
authors.lastname: Bobok
authors.forename: Attila
authors.initials: A
authors.lastname: Horváth
authors.forename: Béla
authors.initials: B
authors.lastname: Kiss
authors.forename: Sándor
authors.initials: S
authors.lastname: Kolok
authors.forename: József
authors.initials: J
authors.lastname: Nagy
authors.forename: Dalma
authors.initials: D
authors.lastname: Kurkó
authors.forename: Mónika L
authors.initials: ML
authors.lastname: Bakk
authors.forename: Mónika
authors.initials: M
authors.lastname: Vastag
authors.forename: Katalin
authors.initials: K
authors.lastname: Sághy
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
authors.forename: Krisztina
authors.initials: K
authors.lastname: Gál
authors.forename: István
authors.initials: I
authors.lastname: Greiner
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szombathelyi
authors.forename: György M
authors.initials: GM
authors.lastname: Keseru
authors.forename: György
authors.initials: G
authors.lastname: Domány
mesh_terms: D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D002219:Carbamates; C578937:Grm5 protein, rat; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine