title: An uncharged oxetanyl sulfoxide as a covalent modifier for improving aqueous solubility.
abstract: Low aqueous solubility is a common challenge in drug discovery and development and can lead to inconclusive biological assay results. Attaching small, polar groups that do not interfere with the bioactivity of the pharmacophore often improves solubility, but there is a dearth of viable neutral moieties available for this purpose. We have modified several poorly soluble drugs or drug candidates with the oxetanyl sulfoxide moiety of 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.
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Skoda
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sacher
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Mustafa Z
authors.initials: MZ
authors.lastname: Kazancioglu
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Saha
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
keywords: Aqueous solubility; JP4-039; MMS-350; oxetane; sulfoxide