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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation
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Animals
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Benzothiadiazines
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Cognition / drug effects
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Cyclic S-Oxides / chemical synthesis*
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Cyclic S-Oxides / chemistry
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Cyclic S-Oxides / pharmacology
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Drug Design
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Electric Stimulation
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Excitatory Postsynaptic Potentials
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Hippocampus / drug effects
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Hippocampus / physiology
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In Vitro Techniques
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Norepinephrine / metabolism
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Oocytes / drug effects
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Oocytes / physiology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism*
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Recognition, Psychology / drug effects
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Structure-Activity Relationship
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Thiadiazines / chemical synthesis*
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Thiadiazines / chemistry
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Thiadiazines / pharmacology
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Xenopus
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
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Benzothiadiazines
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Cyclic S-Oxides
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RNA, Messenger
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Receptors, AMPA
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Thiadiazines
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Norepinephrine