Experimental and Virtual Physicochemical and Pharmacokinetic Profiling of New Chemical Entities

Physicochemical and pharmacokinetic profiling of new chemical entities (NCEs) allows the rapid identification and elimination of compounds with properties not suitable for further development as drug candidates. Among the complex panel of theoretical and experimental methods available to predict or measure physicochemical or pharmacokinetic properties, some key techniques developed or tested in the pharmacochemistry group at EPGL are presented. This paper focuses on virtual and experimental approaches dealing with key properties such as ionization, solubility, lipophilicity, and membrane permeation. In addition, the effect of the third dimension on intramolecular interactions is exemplified by lipophilicity variations in the conformational space of cyclosporin A and with a 3D solvatochromic model able to accurately predict the BBB permeation