Document Report Card

ID: ALA1125342

Journal: J Med Chem

Title: Condensation of muscimol or thiomuscimol with aminopyridazines yields GABA-A antagonists.

Authors: Melikian A, Schlewer G, Chambon JP, Wermuth CG.

Abstract: 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.

CiteXplore: 1331456

DOI: 10.1021/jm00100a015