Solubility-driven lead optimisation: Recent examples and personal perspectives

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.

Figure optionsDownload as PowerPoint slide