Lipophilic Ligand Efficiency as a Useful Metric in Hit and Lead Optimization

Abstract

Traditional medicinal chemistry has directed hits and leads toward larger size and more lipophilic compounds during optimization. Avoiding molecular obesity has been a major challenge in drug discovery. Nowadays, useful metrics are developing to substantially help medicinal chemists to find more efficient ligands of own targets. In this essay, ligand efficiency metrics are introduced and discussed which are used to measure the extent of potency gain of a ligand originating from increasing of its lipophilicity.