Title of article :
Synthesis and potent anticonvulsant activities of 4-oxo-imidazo[1,2-a]indeno[1,2-e]pyrazin-8- and -9-carboxylic (acetic) acid AMPA antagonists
Author/Authors :
Jeremy Pratt، نويسنده , , Patrick Jimonet، نويسنده , , Georg Andrees Bohme، نويسنده , , Alain Boireau، نويسنده , , Dominique Damour، نويسنده , , Marc-Williams Debono، نويسنده , , Arielle Genevois-Borella، نويسنده , , John C. R. Randle، نويسنده , , Yves Ribeill، نويسنده , , Jean-Marie Stutzmann، نويسنده , , Marc Vuilhorgne، نويسنده , , Serge Mignani، نويسنده ,
Abstract :
The over-stimulation of excitatory amino acid receptors such as the glutamate AMPA receptor has been suggested to be associated with neurodegenerative disorders. Here we describe an original series of readily water soluble 4-oxo-imidazo[1,2-a]indeno[1,2-e]pyrazin-8- and -9-carboxylic (acetic) acid derivatives. One of these compounds, 4f, exhibited nanomolar binding affinity, potent competitive antagonism at the ionotropic AMPA receptor and a long duration of anticonvulsant activity after administration by parenteral route in vivo.
