6-Aryl-3-pyrrolidinylpyridines as mGlu5 receptor negative allosteric modulators

Jesse M Weiss; Hermogenes N Jimenez; Guiying Li; Myriam April; Michelle A Uberti; Maria D Bacolod; Robb M Brodbeck; Darío Doller

doi:10.1016/j.bmcl.2011.06.014

6-Aryl-3-pyrrolidinylpyridines as mGlu5 receptor negative allosteric modulators

Bioorg Med Chem Lett. 2011 Aug 15;21(16):4891-9. doi: 10.1016/j.bmcl.2011.06.014. Epub 2011 Jun 17.

Authors

Jesse M Weiss¹, Hermogenes N Jimenez, Guiying Li, Myriam April, Michelle A Uberti, Maria D Bacolod, Robb M Brodbeck, Darío Doller

Affiliation

¹ Chemical & Pharmacokinetic Sciences, Lundbeck Research USA, 215 College Road, Paramus, NJ 07652, USA.

PMID: 21757343
DOI: 10.1016/j.bmcl.2011.06.014

Abstract

A series of 6-aryl-3-pyrrolidinylpyridine analogs was explored as structurally novel negative allosteric modulators of the mGlu5 receptor lacking an alkyne or oxadiazole moiety. Compounds in this series were characterized by tractable SAR, good in vitro potencies and brain penetration in rodents.

MeSH terms

Animals
Dose-Response Relationship, Drug
HEK293 Cells
Humans
Models, Molecular
Molecular Structure
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / pharmacology*
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry
Pyrrolidines / pharmacology*
Rats
Rats, Sprague-Dawley
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Receptors, Metabotropic Glutamate / blood
Stereoisomerism
Structure-Activity Relationship

Substances

Pyridines
Pyrrolidines
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate