Discovery of 1H-pyrrolo[2,3-c]pyridine-7-carboxamides as novel, allosteric mGluR5 antagonists

Manuel Koller; David A Carcache; David Orain; Peter Ertl; Dirk Behnke; Sandrine Desrayaud; Grit Laue; Ivo Vranesic

doi:10.1016/j.bmcl.2012.08.053

Discovery of 1H-pyrrolo[2,3-c]pyridine-7-carboxamides as novel, allosteric mGluR5 antagonists

Bioorg Med Chem Lett. 2012 Oct 15;22(20):6454-9. doi: 10.1016/j.bmcl.2012.08.053. Epub 2012 Aug 21.

Authors

Manuel Koller¹, David A Carcache, David Orain, Peter Ertl, Dirk Behnke, Sandrine Desrayaud, Grit Laue, Ivo Vranesic

Affiliation

¹ Novartis Institutes for BioMedical Research, Global Discovery Chemistry, 4002 Basel, Switzerland. [email protected]

PMID: 22963764
DOI: 10.1016/j.bmcl.2012.08.053

Abstract

1H-pyrrolo[2,3-c]pyridine-7-carboxamides constitute a new series of allosteric mGluR5 antagonists. Variation of the substituents attached to the heterocyclic scaffold allowed to improve the physico-chemical parameters for optimization of the aqueous solubility while retaining high in vitro potency.

MeSH terms

Allosteric Regulation / drug effects
Amides / chemistry*
Amides / pharmacology*
Drug Discovery
Humans
Inhibitory Concentration 50
Pyridones / chemistry*
Pyridones / pharmacology*
Pyrroles / chemistry
Pyrroles / pharmacology
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Receptors, Metabotropic Glutamate / metabolism
Solubility

Substances

Amides
GRM5 protein, human
Pyridones
Pyrroles
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate