Novel isothiourea derivatives as potent neuroprotectors and cognition enhancers: synthesis, biological and physicochemical properties

Abstract

Various salts of 3-allyl-1,1-dibenzyl-2-ethyl-isothiourea, 1 (hydrochloride), 2 (hydrobromide), and 3 (hydroiodide), were synthesized. Ca-blocking properties of these salts were studied. Comparative analysis of the potentiating effects of 3 and cyclothiazide (CT) on transmembrane currents caused by kainic acid (KA) and glutamate in Purkinje neurons was performed. Analysis of the effects of 1 on N-methyl-D-aspartate (NMDA) receptors was performed on primary culture of heterogeneous neurons of rat cerebral cortex. Single crystals were grown and X-ray diffraction experiments solving the crystal structures of 1-3 were carried out. Analysis of conformations of the molecules in the crystal lattices was performed. The temperature dependencies of the solubility of 1-3 in water and n-octanol were obtained, and the thermodynamic parameters of solubility process were calculated. The effect of halogen atoms on the solubility was analyzed. The partitioning processes in the water-octanol system were studied at 25 degrees C. Chemical stability of tested salts in pH 7.4 phosphate buffer was determined at 25 degrees C.