Fused tricyclic mGluR1 antagonists for the treatment of neuropathic pain

Chad E Bennett; Duane A Burnett; William J Greenlee; Chad E Knutson; Peter Korakas; Cheng Li; Deen Tulshian; Wen-Lian Wu; Rosalia Bertorelli; Silva Fredduzzi; Mariagrazia Grilli; Gianluca Lozza; Angelo Reggiani; Alessio Veltri

doi:10.1016/j.bmcl.2011.12.131

Fused tricyclic mGluR1 antagonists for the treatment of neuropathic pain

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1575-8. doi: 10.1016/j.bmcl.2011.12.131. Epub 2012 Jan 3.

Authors

Chad E Bennett¹, Duane A Burnett, William J Greenlee, Chad E Knutson, Peter Korakas, Cheng Li, Deen Tulshian, Wen-Lian Wu, Rosalia Bertorelli, Silva Fredduzzi, Mariagrazia Grilli, Gianluca Lozza, Angelo Reggiani, Alessio Veltri

Affiliation

¹ Merck Research Laboratories, Kenilworth, NJ 07033-0539, USA. chadbennett3@yahoo.com

PMID: 22266036
DOI: 10.1016/j.bmcl.2011.12.131

Abstract

A series of fused tricyclic mGluR1 antagonists containing a pyridone ring were synthesized. In vitro, these antagonists were potent against both human and rat isozymes, as well as selective for inhibiting mGluR1 over mGluR5. When dosed orally, several examples were active in vivo in a rat SNL test.

MeSH terms

Administration, Oral
Analgesics / pharmacology
Animals
Cells, Cultured
Cyclization
Humans
Inhibitory Concentration 50
Molecular Structure
Neuralgia / drug therapy
Protein Binding / drug effects
Pyridones / chemical synthesis*
Pyridones / chemistry
Pyridones / pharmacology
Rats
Receptors, Metabotropic Glutamate / antagonists & inhibitors*

Substances

Analgesics
Pyridones
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor type 1