Arylmethoxypyridines as novel, potent and orally active mGlu5 receptor antagonists

Bernd Büttelmann; Jens-Uwe Peters; Simona Ceccarelli; Sabine Kolczewski; Eric Vieira; Eric P Prinssen; Will Spooren; Franz Schuler; Jörg Huwyler; Richard H P Porter; Georg Jaeschke

doi:10.1016/j.bmcl.2005.12.088

Arylmethoxypyridines as novel, potent and orally active mGlu5 receptor antagonists

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1892-7. doi: 10.1016/j.bmcl.2005.12.088. Epub 2006 Jan 24.

Authors

Bernd Büttelmann¹, Jens-Uwe Peters, Simona Ceccarelli, Sabine Kolczewski, Eric Vieira, Eric P Prinssen, Will Spooren, Franz Schuler, Jörg Huwyler, Richard H P Porter, Georg Jaeschke

Affiliation

¹ Pharma Division, Discovery Chemistry, F. Hoffman-La Roche Ltd, CH-4070 Basel, Switzerland.

PMID: 16439120
DOI: 10.1016/j.bmcl.2005.12.088

Abstract

Optimisation of affinity, chemical stability, metabolic stability and solubility led from a chemically labile HTS hit 1 to mGlu5 receptor antagonists (24-26) with high affinity for the allosteric MPEP binding site, improved microsomal metabolic stability and anxiolytic-like activity in vivo as assessed by the Vogel conflict drinking test.

MeSH terms

Administration, Oral
Excitatory Amino Acid Antagonists / administration & dosage
Excitatory Amino Acid Antagonists / chemistry
Excitatory Amino Acid Antagonists / pharmacology*
Pyridines / administration & dosage
Pyridines / chemistry
Pyridines / pharmacology*
Receptors, Metabotropic Glutamate / antagonists & inhibitors*

Substances

Excitatory Amino Acid Antagonists
Pyridines
Receptors, Metabotropic Glutamate