An uncharged oxetanyl sulfoxide as a covalent modifier for improving aqueous solubility.

Low aqueous solubility is a common challenge in drug discoveryand development and can lead to inconclusive biological assay results. Attaching small, polar groups that do not interfere with the bioactivity of the pharmacophoreoften improves solubility, but there is a dearth of viable neutral moietiesavailable for this purpose. We have modified several poorly soluble drugs or drug candidates with the oxetanyl sulfoxide moietyof the DMSO analog MMS-350 and noted in most cases a moderate to large improvement of aqueous solubility. Furthermore, the membrane permeability of a test sample was enhanced compared to the parent compound.