Quinazolinedione sulfonamides: a novel class of competitive AMPA receptor antagonists with oral activity

Manuel Koller; Kurt Lingenhoehl; Markus Schmutz; Ivan-Toma Vranesic; Joerg Kallen; Yves P Auberson; David A Carcache; Henri Mattes; Silvio Ofner; David Orain; Stephan Urwyler

doi:10.1016/j.bmcl.2011.04.017

Quinazolinedione sulfonamides: a novel class of competitive AMPA receptor antagonists with oral activity

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3358-61. doi: 10.1016/j.bmcl.2011.04.017. Epub 2011 Apr 8.

Authors

Manuel Koller¹, Kurt Lingenhoehl, Markus Schmutz, Ivan-Toma Vranesic, Joerg Kallen, Yves P Auberson, David A Carcache, Henri Mattes, Silvio Ofner, David Orain, Stephan Urwyler

Affiliation

¹ Novartis Institutes for BioMedical Research, Global Discovery Chemistry, 4002 Basel, Switzerland. manuel.koller@novartis.com

PMID: 21531559
DOI: 10.1016/j.bmcl.2011.04.017

Abstract

Quinazoline-2,4-diones with a sulfonamide group attached to the N(3) ring atom constitute a novel class of competitive AMPA receptor antagonists. One of the synthesized compounds, 28, shows nanomolar receptor affinity, whereas other examples of the series display oral anticonvulsant activity in animal models.

MeSH terms

Administration, Oral
Animals
Anticonvulsants / pharmacology
Binding, Competitive / drug effects
Crystallography, X-Ray
Mice
Molecular Structure
Quinazolinones / chemical synthesis*
Quinazolinones / chemistry
Quinazolinones / pharmacology
Rats
Receptors, AMPA / antagonists & inhibitors*
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacology

Substances

Anticonvulsants
Quinazolinones
Receptors, AMPA
Sulfonamides