Structure-activity relationships of novel non-competitive mGluR1 antagonists: a potential treatment for chronic pain

Dafydd R Owen; Peter G Dodd; Simon Gayton; Ben S Greener; Gareth W Harbottle; Simon J Mantell; Graham N Maw; Simon A Osborne; Huw Rees; Tracy J Ringer; Margarita Rodriguez-Lens; Graham F Smith

doi:10.1016/j.bmcl.2006.10.015

Structure-activity relationships of novel non-competitive mGluR1 antagonists: a potential treatment for chronic pain

Bioorg Med Chem Lett. 2007 Jan 15;17(2):486-90. doi: 10.1016/j.bmcl.2006.10.015. Epub 2006 Oct 11.

Authors

Dafydd R Owen¹, Peter G Dodd, Simon Gayton, Ben S Greener, Gareth W Harbottle, Simon J Mantell, Graham N Maw, Simon A Osborne, Huw Rees, Tracy J Ringer, Margarita Rodriguez-Lens, Graham F Smith

Affiliation

¹ Pfizer Global Research and Development, Ramsgate Road, Sandwich, CT13 9NJ, UK. [email protected]

PMID: 17064898
DOI: 10.1016/j.bmcl.2006.10.015

Abstract

A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driven second library iteration, covering a greatly enhanced area of chemical space, maintained good potency and introduced metabolic stability.

MeSH terms

Animals
Binding, Competitive / drug effects
CHO Cells
Chemical Phenomena
Chemistry, Physical
Chronic Disease
Cricetinae
Cricetulus
Dose-Response Relationship, Drug
Glutamic Acid / pharmacology
Pain / drug therapy*
Pyrazines / chemical synthesis
Pyrazines / pharmacology
Rats
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Pyrazines
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor type 1
Glutamic Acid