6-Amino quinazolinedione sulfonamides as orally active competitive AMPA receptor antagonists

David Orain; Silvio Ofner; Manuel Koller; David A Carcache; Wolfgang Froestl; Hans Allgeier; Vittorio Rasetti; Joachim Nozulak; Henri Mattes; Nicolas Soldermann; Philipp Floersheim; Sandrine Desrayaud; Joerg Kallen; Kurt Lingenhoehl; Stephan Urwyler

doi:10.1016/j.bmcl.2011.12.009

6-Amino quinazolinedione sulfonamides as orally active competitive AMPA receptor antagonists

Bioorg Med Chem Lett. 2012 Jan 15;22(2):996-9. doi: 10.1016/j.bmcl.2011.12.009. Epub 2011 Dec 8.

Authors

David Orain¹, Silvio Ofner, Manuel Koller, David A Carcache, Wolfgang Froestl, Hans Allgeier, Vittorio Rasetti, Joachim Nozulak, Henri Mattes, Nicolas Soldermann, Philipp Floersheim, Sandrine Desrayaud, Joerg Kallen, Kurt Lingenhoehl, Stephan Urwyler

Affiliation

¹ Novartis Institute for Biomedical Research, Global Discovery Chemistry, Basel CH-4002, Switzerland. david.orain@novartis.com

PMID: 22197388
DOI: 10.1016/j.bmcl.2011.12.009

Abstract

A new set of quinazolinedione sulfonamide derivatives as competitive AMPA receptor antagonist with improved properties compared to 1 is disclosed. By modulating physico-chemical properties, compound 29 was identified with a low ED(50) of 5.5mg/kg in an animal model of anticonvulsant activity after oral dosage.

MeSH terms

Administration, Oral
Animals
Anticonvulsants / administration & dosage
Anticonvulsants / chemistry
Anticonvulsants / pharmacology*
Crystallography, X-Ray
Disease Models, Animal
Dose-Response Relationship, Drug
Mice
Mice, Inbred DBA
Models, Molecular
Molecular Structure
Quinazolinones / administration & dosage
Quinazolinones / chemistry
Quinazolinones / pharmacology*
Receptors, AMPA / antagonists & inhibitors*
Seizures / drug therapy
Stereoisomerism
Structure-Activity Relationship
Sulfonamides / administration & dosage
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Anticonvulsants
Quinazolinones
Receptors, AMPA
Sulfonamides