1 research outputs found
5-Arylbenzothiadiazine Type Compounds as Positive Allosteric Modulators of AMPA/Kainate Receptors
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-2<i>H</i>-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