Abstract We present in this study the synthesis and characterization of a new 3,3-dimethyl-substituted 1,2,4-benzothiadiazine 1,1-dioxide. 3,3-dimethyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide 10, was obtained by reacting 2-aminobenzenesulfonamide with acetone. The molecular structures of… Click to show full abstract
Abstract We present in this study the synthesis and characterization of a new 3,3-dimethyl-substituted 1,2,4-benzothiadiazine 1,1-dioxide. 3,3-dimethyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide 10, was obtained by reacting 2-aminobenzenesulfonamide with acetone. The molecular structures of the starting sulfonamide and the new benzothiadiazine were obtained by X-ray diffraction analysis and the interactions like hydrogen bonds stabilizing the crystal packing were discussed. The contacts are confirmed by non-covalent interaction analysis. Analyses of Hirshfeld surface mapped over di, de, dnorm and shape-index were further used to identify the intermolecular interactions. The fingerprint histogram allow to show that H•••H (45.7%) and O•••H (30.1%) contacts are the dominant interactions in the crystal packing of 10. The effects of the molecular environment were accessed by analyzing the electron density isosurface and the 3D-topology of energy frameworks. The prediction of physicochemical properties suggested that 10 could be considered as a lead-like drug. Therefore, molecular docking study was performed on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and suggested that 10 could interact with the allosteric site located on the ligand binding domain of AMPAR and could be a positive allosteric modulator. Docking results show that 10 can bind in a symmetrical way in the GluA2 ligand binding domain with two molecules at the dimer interface. The results also demonstrated that the presence of two methyl groups at the 3-position of the thiadiazine ring induced rotation of 10 in the binding site leading to close contacts with Pro494, Ser497, Ser729 and Ser754.
               
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