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

详细信息    查看全文

• 作者：Pierre Francotte ; Pascal de Tullio ; Eric Goffin ; Gaë ; lle Dintilhac ; Emmanuel Graindorge ; Pierre Fraikin ; Pierre Lestage ; Laurence Danober ; Jean-Yves Thomas ; Daniel-Henri Caignard ; Bernard Pirotte
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：June 28, 2007
• 年：2007
• 卷：50
• 期：13
• 页码：3153 - 3157
• 全文大小：93K
• 年卷期：v.50,no.13(June 28, 2007)
• ISSN：1520-4804

文摘

A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated aspotentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the7-position of the heterocycle. The biological evaluation was achieved by measuring the AMPA current inrat 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 ratsdemonstrating cognition enhancing effects in vivo after oral administration.