In Vitro and in Vivo SAR of Pyrido[3,4-d]pyramid-4-ylamine Based MGluR1 Antagonists

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2009 Mar 18

PMID 19289283

Citations 6

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

N-Alkylpyrido[1',2':1,5]pyrazolo-[4,3-d]pyrimidin-4-amines: A new series of negative allosteric modulators of mGlu1/5 with CNS exposure in rodents.

Felts A, Rodriguez A, Morrison R, Venable D, Blobaum A, Byers F Bioorg Med Chem Lett. 2016; 26(8):1894-900.

PMID: 26988308 PMC: 4824313. DOI: 10.1016/j.bmcl.2016.03.026.

A novel class of succinimide-derived negative allosteric modulators of metabotropic glutamate receptor subtype 1 provides insight into a disconnect in activity between the rat and human receptors.

Cho H, Engers D, Venable D, Niswender C, Lindsley C, Conn P ACS Chem Neurosci. 2014; 5(7):597-610.

PMID: 24798819 PMC: 4102972. DOI: 10.1021/cn5000343.

Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1.

Manka J, Rodriguez A, Morrison R, Venable D, Cho H, Blobaum A Bioorg Med Chem Lett. 2013; 23(18):5091-6.

PMID: 23932792 PMC: 3901432. DOI: 10.1016/j.bmcl.2013.07.029.

N-Acyl-N'-arylpiperazines as negative allosteric modulators of mGlu1: identification of VU0469650, a potent and selective tool compound with CNS exposure in rats.

Lovell K, Felts A, Rodriguez A, Venable D, Cho H, Morrison R Bioorg Med Chem Lett. 2013; 23(13):3713-8.

PMID: 23727046 PMC: 3875306. DOI: 10.1016/j.bmcl.2013.05.020.

Recent advances in the medicinal chemistry of the metabotropic glutamate receptor 1 (mGlu₁).

Owen D ACS Chem Neurosci. 2012; 2(8):394-401.

PMID: 22860168 PMC: 3369754. DOI: 10.1021/cn2000124.