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
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 curr...
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Published in | Journal of medicinal chemistry Vol. 50; no. 13; pp. 3153 - 3157 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article Web Resource |
Language | English |
Published |
WASHINGTON
American Chemical Society
28.06.2007
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | istex:E9E839E111F586700594A19C1B79135C9FD3435E ark:/67375/TPS-3HDCNBC8-T This paper is dedicated to the memory of Prof. J. Delarge. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 scopus-id:2-s2.0-34347213071 |
ISSN: | 0022-2623 1520-4804 1520-4804 |
DOI: | 10.1021/jm070120i |