Physicochemical Parameters of Recently Approved Oral Drugs
Andreas Ritzén, Laurent David · 2019
This chapter presents an analysis of the distribution of six key properties for all 175 orally dosed drugs with systemic action that were approved by the United States Food and Drug Administration in 2007–2017. The properties analyzed are molecular weight, topological polar surface area (TPSA), predicted log P, number of hydrogen bond acceptors, number of hydrogen bond donors, and number of rotatable bonds. It has been suggested that large, polar beyond rule of five molecules must be chameleonic to be orally bioavailable: They expose polarity in aqueous environments to aid solubility, but they bury polar groups by intramolecular hydrogen bonding in the lipid environment of biological membranes to achieve good permeability. To explore this phenomenon, the chapter undertooks molecular dynamics simulations of selected examples in explicit solvents. The widely used TPSA parameter is based on the two-dimensional representation of the molecule.