Document Report Card

ID: ALA1145399

Journal: J Med Chem

Title: Design, synthesis, and pharmacology of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors.

Authors: Francotte P, Tullio Pd, Goffin E, Dintilhac G, Graindorge E, Fraikin P, Lestage P, Danober L, Thomas JY, Caignard DH, Pirotte B.

Abstract: A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the 7-position of the heterocycle. The biological evaluation was achieved by measuring the AMPA current in rat cortex mRNA-injected Xenopus oocytes. The most potent compound, 4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in an object recognition test in rats demonstrating cognition enhancing effects in vivo after oral administration.

CiteXplore: 17552506

DOI: 10.1021/jm070120i