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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.

SUBMITTER: Skoda EM

PROVIDER: S-EPMC4137373 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Skoda Erin M EM Sacher Joshua R JR Kazancioglu Mustafa Z MZ Saha Jaideep J Wipf Peter P

ACS medicinal chemistry letters 20140627 8

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 lar ...[more]

PMID: 25147611

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