Article date: 1992/10/30
PubMed ID: 1331456
Journal name: Journal of medicinal chemistry (ISSN: 0022-2623)
Ten analogs of muscimol and thiomuscimol in which the amino function was delocalized in an amidinic system were prepared by N2 alkylation of 6-aryl-3-aminopyridazines with (chloromethyl)isoxazole or (chloromethyl)isothiazole derivatives. These muscimol and thiomuscimol derivatives show potent binding properties for GABA-A receptors (they displace [3H]GABA and [3H]gabazine) and provoke convulsions after iv injections. They fit well with the model pharmacophore proposed by our group for the GABA-A antagonists and show similar structure-activity profiles to that of the pyridazinyl-GABAs.
Author List: Melikian A, Schlewer G, Chambon J P, Wermuth C G
Publication Types: Journal Article
Substances mentioned in the article: Convulsants; GABA-A Receptor Antagonists; Pyridazines; Receptors, GABA-A; Muscimol; thiomuscimol;
Mesh terms: Animals; Binding, Competitive; Convulsants/chemical synthesis; Female; GABA-A Receptor Antagonists; In Vitro Techniques; Mice; Models, Molecular; Molecular Conformation; Muscimol/analogs & derivatives; Pyridazines/chemical synthesis; Radioligand Assay; Rats; Receptors, GABA-A/metabolism; Structure-Activity Relationship;