54734-82-6Relevant academic research and scientific papers
Derivatives of 1,2,4-benzothiadiazine dioxide, their preparation and use as allosteric modulators of the AMPA receptor
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Page/Page column 9-10, (2012/06/05)
A compound of formula I is described: which showed to be surprisingly and significantly effective as an allosteric modulator of the AMPA receptor and is therefore particularly suitable for the treatment of mnemocognitive disorders ascribable to an alterat
5-arylbenzothiadiazine type compounds as positive allosteric modulators of AMPA/kainate receptors
Battisti, Umberto M.,Jozwiak, Krzysztof,Cannazza, Giuseppe,Puia, Giulia,Stocca, Gabriella,Braghiroli, Daniela,Parenti, Carlo,Brasili, Livio,Carrozzo, Marina M.,Citti, Cinzia,Troisi, Luigino
supporting information; experimental part, p. 25 - 29 (2012/04/04)
The potential therapeutic benefit of compounds able to activate AMPA receptors (AMPAr) has led to the search for new AMPAr positive modulators. On the basis of crystallographic data of the benzothiadiazines binding mode in the S1S2 GluA2 dimer interface, a set of 5-aryl-2,3-dihydrobenzothiadiazine type compounds has been synthesized and tested. Electrophysiological results suggested that 5-heteroaryl substituents on the benzothiadiazine core like 3-furanyl and 3-thiophenyl dramatically enhance the activity as positive modulators of AMPAr with respect to IDRA21 and cyclothiazide. Mouse brain microdialysis studies have suggested that 7-chloro-5-(3-furyl)-3-methyl-3,4- dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide crosses the blood-brain barrier after intraperitoneal injection. Biological results have been rationalized by a computational docking simulation that it has currently employed to design new AMPAr-positive modulator candidates.
