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

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 2; pp. 996 - 999
• Main Authors: Orain, David, Ofner, Silvio, Koller, Manuel, Carcache, David A., Froestl, Wolfgang, Allgeier, Hans, Rasetti, Vittorio, Nozulak, Joachim, Mattes, Henri, Soldermann, Nicolas, Floersheim, Philipp, Desrayaud, Sandrine, Kallen, Joerg, Lingenhoehl, Kurt, Urwyler, Stephan
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-01-2012; Elsevier
• Subjects: Administration, Oral; AMPA receptor antagonist; animal models; Animals; antagonists; Anticonvulsant; anticonvulsants; Anticonvulsants - administration & dosage; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Crystallography, X-Ray; Disease Models, Animal; Dose-Response Relationship, Drug; Glutamate receptors; Medical sciences; Mice; Mice, Inbred DBA; Models, Molecular; Molecular Structure; Neuropharmacology; oral administration; Orally active; Pharmacology. Drug treatments; physicochemical properties; Quinazoline-2,4-dione sulfonamide; Quinazolinones - administration & dosage; Quinazolinones - chemistry; Quinazolinones - pharmacology; Receptors, AMPA - antagonists & inhibitors; Seizures - drug therapy; Stereoisomerism; Structure-Activity Relationship; sulfonamides; Sulfonamides - administration & dosage; Sulfonamides - chemistry; Sulfonamides - pharmacology; Glutamate receptors; Orally active; Anticonvulsant; Quinazoline-2,4-dione sulfonamide; AMPA receptor antagonist; AMPA receptor; Sulfonamide; Sulfonamides; Quinazoline derivatives; Oral administration; Glutamate receptor; Antagonist
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.12.009

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 ED50 of 5.5mg/kg in an animal model of anticonvulsant activity after oral dosage.