Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists

János Galambos; Gábor Wágner; Katalin Nógrádi; Attila Bielik; László Molnár; Amrita Bobok; Attila Horváth; Béla Kiss; Sándor Kolok; József Nagy; Dalma Kurkó; Mónika L Bakk; Mónika Vastag; Katalin Sághy; István Gyertyán; Krisztina Gál; István Greiner; Zsolt Szombathelyi; György M Keseru; György Domány

doi:10.1016/j.bmcl.2010.06.075

Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4371-5. doi: 10.1016/j.bmcl.2010.06.075. Epub 2010 Jun 17.

Affiliation

¹ Gedeon Richter Plc, Budapest, Hungary.

PMID: 20615697
DOI: 10.1016/j.bmcl.2010.06.075

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.

MeSH terms

Animals
Carbamates / chemical synthesis
Carbamates / chemistry*
Carbamates / pharmacology
High-Throughput Screening Assays
Oximes / chemical synthesis
Oximes / chemistry*
Oximes / pharmacology
Pyridines / chemistry
Pyridines / pharmacology
Rats
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Receptors, Metabotropic Glutamate / metabolism
Substrate Specificity

Substances

Carbamates
Grm5 protein, rat
Oximes
Pyridines
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate
6-methyl-2-(phenylethynyl)pyridine