Solubility in Pharmaceutical R&D:Predictions and Reality

摘要

Lipinski's seminal paper on experimental and computational {insilico) methods to estimate the solubility and permeability of drug candidates was published just over 15-years ago [1]. Theiconic'Ruleof5'predicted that absorption was adversely impacted when the calculated LogP (cLogP) was greater than 5, when molecular weight (MW) was greater than 500, when there are greater than 5 H-bond donors or greater than 10 H-bond acceptors.The related concept of'drug-likeness'importantly focuses on both potency and physicochemical attributes, using tools such as lipophilic efficiency [2] or ligand efficiency [3].