Noerholm, Ann-Beth published the artcileSynthesis, Pharmacological and Structural Characterization, and Thermodynamic Aspects of GluA2-Positive Allosteric Modulators with a 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxide Scaffold, Formula: C10H11FN2O2S, the publication is Journal of Medicinal Chemistry (2013), 56(21), 8736-8745, database is CAplus and MEDLINE.
Pos. allosteric modulators of ionotropic glutamate receptors are potential compounds for treatment of cognitive disorders, e.g., Alzheimer’s disease. The modulators bind within the dimer interface of the ligand-binding domain (LBD) and stabilize the agonist-bound conformation, thereby slowing receptor desensitization and/or deactivation. Here we describe the synthesis and pharmacol. testing at GluA2 of a new generation of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides. The most potent modulator I in complex with GluA2-LBD-L483Y-N754S was subjected to structural anal. by X-ray crystallog., and the thermodn. of binding was studied by isothermal titration calorimetry. Compound I binds to GluA2-LBD-L483Y-N754S with a Kd of 0.35 μM (ΔH = -7.5 kcal/mol and -TΔS = -1.3 kcal/mol). This is the first time that submicromolar binding affinity has been achieved for this type of pos. allosteric modulator. The major structural factor increasing the binding affinity of I seems to be interactions between the cyclopropyl group of I and the backbone of Phe495 and Met496.
Journal of Medicinal Chemistry published new progress about 1204572-55-3. 1204572-55-3 belongs to thiazole, auxiliary class Neuronal Signaling,GluR, name is 4-Cyclopropyl-7-fluoro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide, and the molecular formula is C10H11FN2O2S, Formula: C10H11FN2O2S.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica