Noerholm, Ann-Beth published the artcileThermodynamic Characterization of New Positive Allosteric Modulators Binding to the Glutamate Receptor A2 Ligand-Binding Domain: Combining Experimental and Computational Methods Unravels Differences in Driving Forces, Name: 4-Cyclopropyl-7-fluoro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide, the publication is Journal of Chemical Information and Modeling (2014), 54(12), 3404-3416, database is CAplus and MEDLINE.
Pos. allosteric modulation of the ionotropic glutamate receptor GluA2 presents a potential treatment of cognitive disorders, for example, Alzheimer’s disease. In the present study, the authors describe the synthesis, pharmacol., and thermodn. studies of a series of monofluoro-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides I [R = 5-F, 6-F, 7-F, 8-F]. Measurements of ligand binding by isothermal titration calorimetry (ITC) showed similar binding affinities for the modulator series at the GluA2 LBD but differences in the thermodn. driving forces. Binding of I [R = 7-F] and I [R = H] is enthalpy driven, and I [R = 5-F] and I [R = 6-F] are entropy driven. For I [R = 8-F], both quantities were equal in size. Thermodn. integration (TI) and one-step perturbation (OSP) were used to calculate the relative binding affinity of the modulators. The OSP calculations had a higher predictive power than those from TI, and combined with the shorter total simulation time, the authors found the OSP method to be more effective for this setup. Furthermore, from the mol. dynamics simulations, the authors extracted the enthalpies and entropies, and along with the ITC data, this suggested that the differences in binding free energies are largely explained by the direct ligand-surrounding enthalpies. Furthermore, the authors used the OSP setup to predict binding affinities for a series of polysubstituted fluorine compounds and monosubstituted Me compounds and used these predictions to characterize the modulator binding pocket for this scaffold of pos. allosteric modulators.
Journal of Chemical Information and Modeling 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, Name: 4-Cyclopropyl-7-fluoro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica