Abstract

In recent years, in silico pharmaceutical tools have a notable impact of drug discovery as complementary methods for in vitro and in vivo assays. Such procedures help to optimize pharmacokinetic and pharmaceutical properties of (not only) drug-like candidates. Following the Lipinski#xB4;s Rule of Five concept and experimental partition coefficients data as well, the majority of currently in silico investigated compounds, 8aB#x2013;8iB, which structure contained so-called privileged structure, 4-(3-trifluoromethylphenyl)piperazin-1-yl fragment, would be regarded as the drugs with the physicochemical properties that could be convenient in terms of their pharmacokinetic and metabolic profiles. In addition, their ability to cross blood#x2013;brain barrier was in silico inspected. In general, the CNS drugs tend to be more lipophilic, be less polar, have shown less flexibility, had lower molecular weight and smaller molecular volume as well than the drugs applied for other therapeutic indications. Following the calculated (molecular weight, topological polar surface area, hydrogenbond acceptors count, hydrogen-bond donors count, rotatable bonds count, CLOGP data) and experimentally estimated (log Pexp) readouts, it was suggested that concerned derivatives would probably not cross blood#x2013;brain barrier by passive diffusion, thus they could not affect CNS processes.