Tricyclic thienopyridine-pyrimidones/thienopyrimidine-pyrimidones as orally efficacious mGluR1 antagonists for neuropathic pain

T K Sasikumar; Li Qiang; Duane A Burnett; William J Greenlee; Cheng Li; Larry Heimark; Birendra Pramanik; Mariagrazia Grilli; Rosalia Bertorelli; Gianluca Lozza; Angelo Reggiani

doi:10.1016/j.bmcl.2009.04.104

Tricyclic thienopyridine-pyrimidones/thienopyrimidine-pyrimidones as orally efficacious mGluR1 antagonists for neuropathic pain

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3199-203. doi: 10.1016/j.bmcl.2009.04.104. Epub 2009 May 3.

Authors

T K Sasikumar¹, Li Qiang, Duane A Burnett, William J Greenlee, Cheng Li, Larry Heimark, Birendra Pramanik, Mariagrazia Grilli, Rosalia Bertorelli, Gianluca Lozza, Angelo Reggiani

Affiliation

¹ Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. sasikumartk@yahoo.com

PMID: 19433355
DOI: 10.1016/j.bmcl.2009.04.104

Abstract

Introduction of small unsaturated alkylamino groups at the 4-position of the A-ring of the tricyclic framework (triazafluorenone) afforded extremely potent and selective mGluR1 antagonists with desirable properties. Compounds 11q and 11s are active in the SNL pain model with ED(50)s 3.3 and 6.4 mg/kg respectively. Metabolic outcome of propargyl amino moiety was studied.

MeSH terms

Administration, Oral
Animals
Dose-Response Relationship, Drug
Heterocyclic Compounds, 3-Ring / chemistry
Heterocyclic Compounds, 3-Ring / pharmacology
Humans
Inhibitory Concentration 50
Neuralgia / drug therapy*
Pyridines / chemistry*
Pyridines / pharmacology
Pyrimidines / chemistry*
Pyrimidines / pharmacology
Rats
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Heterocyclic Compounds, 3-Ring
Pyridines
Pyrimidines
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor type 1
thienopyridine
thienopyrimidine