Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists.
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.
Galambos
János
J
Gedeon Richter Plc, Budapest, Hungary.
Wágner
Gábor
G
Nógrádi
Katalin
K
Bielik
Attila
A
Molnár
László
L
Bobok
Amrita
A
Horváth
Attila
A
Kiss
Béla
B
Kolok
Sándor
S
Nagy
József
J
Kurkó
Dalma
D
Bakk
Mónika L
ML
Vastag
Mónika
M
Sághy
Katalin
K
Gyertyán
István
I
Gál
Krisztina
K
Greiner
István
I
Szombathelyi
Zsolt
Z
Keseru
György M
GM
Domány
György
G
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
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