Synthesis and characterization of 8-ethynyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: new potent non-competitive metabotropic glutamate receptor 2/3 antagonists. Part 1

Thomas J Woltering; Geo Adam; Alexander Alanine; Jürgen Wichmann; Frédéric Knoflach; Vincent Mutel; Silvia Gatti

doi:10.1016/j.bmcl.2007.10.026

Synthesis and characterization of 8-ethynyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: new potent non-competitive metabotropic glutamate receptor 2/3 antagonists. Part 1

Bioorg Med Chem Lett. 2007 Dec 15;17(24):6811-5. doi: 10.1016/j.bmcl.2007.10.026. Epub 2007 Oct 17.

Authors

Thomas J Woltering¹, Geo Adam, Alexander Alanine, Jürgen Wichmann, Frédéric Knoflach, Vincent Mutel, Silvia Gatti

Affiliation

¹ F. Hoffmann-La Roche Ltd, Pharma Discovery Chemistry, CNS CH-4070 Basel, Switzerland.

PMID: 17964783
DOI: 10.1016/j.bmcl.2007.10.026

Abstract

A series of 1,3-dihydrobenzo[b][1,4]diazepin-2-one derivatives was evaluated as non-competitive mGluR2/3 antagonists. Attachment of an 8-(2-aryl)-ethynyl-moiety produced compounds inhibiting the binding of [(3)H]-LY354740 to rat mGluR2 with low nanomolar affinity and consistent functional effect at both mGluR2 and mGluR3.

MeSH terms

Animals
Azepines / chemical synthesis*
Azepines / chemistry
Azepines / pharmacology*
CHO Cells
Cricetinae
Cricetulus
Molecular Structure
Rats
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Receptors, Metabotropic Glutamate / metabolism*

Substances

8-ethynyl-1,3-dihydro-benzo(b)(1,4)diazepin-2-one
Azepines
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor 2
metabotropic glutamate receptor 3