In vitro and in vivo SAR of pyrido[3,4-d]pyramid-4-ylamine based mGluR1 antagonists

Simon J Mantell; Karl R Gibson; Simon A Osborne; Graham N Maw; Huw Rees; Peter G Dodd; Ben Greener; Gareth W Harbottle; William A Million; Cedric Poinsard; Steven England; Pauline Carnell; Alison M Betts; Russell Monhemius; Rebecca L Prime

doi:10.1016/j.bmcl.2009.02.106

In vitro and in vivo SAR of pyrido[3,4-d]pyramid-4-ylamine based mGluR1 antagonists

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2190-4. doi: 10.1016/j.bmcl.2009.02.106. Epub 2009 Mar 3.

Authors

Simon J Mantell¹, Karl R Gibson, Simon A Osborne, Graham N Maw, Huw Rees, Peter G Dodd, Ben Greener, Gareth W Harbottle, William A Million, Cedric Poinsard, Steven England, Pauline Carnell, Alison M Betts, Russell Monhemius, Rebecca L Prime

Affiliation

¹ Drug Discovery Group, Medical Research Council Technology, Mill Hill, London, United Kingdom. [email protected]

PMID: 19289283
DOI: 10.1016/j.bmcl.2009.02.106

Abstract

The SAR of a series of novel pyrido[3,4-d]pyramid-4-ylamine mGluR1 antagonists is described. The multiple of the unbound K(i) in cerebrospinal fluid necessary to give morphine like analgesic effects in an electromyograph pinch model in rodents is determined and the effect of structure on CNS penetration examined.

Publication types

Comparative Study

MeSH terms

Animals
Electromyography / methods
Excitatory Amino Acid Antagonists / chemical synthesis*
Excitatory Amino Acid Antagonists / chemistry
Excitatory Amino Acid Antagonists / pharmacology
Pain Measurement / drug effects
Pain Measurement / methods
Rats
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Receptors, Metabotropic Glutamate / physiology
Structure-Activity Relationship

Substances

Excitatory Amino Acid Antagonists
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor type 1