Optimisation of aqueous solubility in a series of G protein coupled receptor 119 (GPR119) agonistsThis article is part of a MedChemComm 'New Talents' issue highlighting the work of outstanding rising scientists in medicinal chemistry research.Electronic supplementary information (ESI) available: Synthetic details for the synthesis of 11 and crystallographic data for 13. See DOI: 10.1039/c2md20130e

Improving aqueous solubility is a challenge frequently faced within drug discovery programs. Herein we describe increases in solubility in two sub-series of GPR119 agonists through reduction of lipophilicity together with hydrogen bond acceptor modulation. Small molecule X-ray crystallography was utilised to investigate effects on solid state interactions. Solubility improvements in a series of GPR119 agonists are achieved through reduction of lipophilicity together with hydrogen bond acceptor modulation.