The Problem of Lipohilicity Medicinal chemists are constantly balancing the physical chemical properties of their target compounds to discover the next successful medicine. Adding lipophilicity improves potency but increases metabolic clearance, reduces aqueous solubility, and is directly proportional to an increase in secondary pharmacology. The Problem of Polarity Conversely, adding polarity often reduces metabolic clearance, increases aqueous solubility and reduces the risk of picking u...