title: Solubility-driven lead optimisation: Recent examples and personal perspectives.
abstract: Solubility is recognised as one of the most important physicochemical parameters necessary for a successful clinical candidate. Despite that, there are few articles in the medicinal chemistry literature with a specific focus on solubility-driven optimisation of lead compounds. This could be because the importance of measuring solubilities as part of the optimisation process is relatively underappreciated, or the fact that obtaining sufficient high quality solubility data is difficult. This review gives examples of solubility-driven optimisation programs from the last fifteen years, and explores recent developments in solubility measurement techniques. Quantitative NMR methods are highlighted; these offer the potential to provide high quality solubility measurements in a cost-effective and high-throughput manner.
authors.affiliation: Vertex Pharmaceuticals, 86-88 Jubilee Avenue, Milton Park, Abingdon OX14 4RY, United Kingdom.
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Ahmad
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D024881:Drug Resistance, Bacterial; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011355:Prodrugs; D002939:Ciprofloxacin
keywords: Kinetic solubility; Solubility; Thermodynamic solubility; qNMR