Towards the rational design of novel drugs based on solubility, partitioning/distribution, biomimetic permeability and biological activity exemplified by 1,2,4-thiadiazole derivatives

Article abstract of DOI:10.1039/c6md00545d

Novel 1,2,4-thiadiazole derivatives as potent neuroprotectors were synthesized and identified. Their ability to inhibit the glutamate stimulated Ca²⁺ uptake was investigated. The solubility of thiadiazoles was measured in a buffer solution (pH 7.4) at 298 K. The distribution coefficients in 1-octanol/buffer (pH 7.4) and 1-hexane/buffer (pH 7.4) immiscible phases as model systems imitating the gastrointestinal tract epithelium and the blood-brain barrier were determined. Permeation experiments the new Permeapad barrier using Franz diffusion cells were conducted and the apparent permeability coefficients were obtained. The influence of the compound structure on the physicochemical properties determining the bioavailability of drug-like substances was revealed. Solubility-permeability interplay has been assessed to evaluate potential bioavailability of the compounds studied.