Lipinski’s rule of five, famous extensions and famous exceptions

Mathematical models show qualitative and quantitative dependencies between the structure, physico- chemical properties and activities of the investigated compounds. There are different rules for the prediction of good bioavailability, and one of the most well-known is the Lipinski rule. The rule is related to the molecular properties important for a drug’s pharmacokinetics in the human body: absorption, distribution, metabolism, and excretion (ADME). In addition to the Lipinski rule, there are reported different combinations of criteria that are important predictors of permeability. An additional rule was proposed by Veber. He compared the oral bioavailability of the compound and the permeability of the compound with the molecular flexibility.