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ID: ALA3868631
Journal: Bioorg Med Chem Lett
Title: Discovery of SOAT2 inhibitors from synthetic small molecules.
Authors: Kobayashi K, Ohshiro T, Tomoda H, Yin F, Cui HL, Chouthaiwale PV, Tanaka F.
Abstract: Synthesis of new functionalized molecules and identification of biofunctional molecules can lead to the development of therapeutic leads and molecular tools for biomedical research. We have recently reported oxa-hetero-Diels-Alder reactions of enones with isatins to provide functionalized spirooxindole tetrahydropyran derivatives. Twenty-one compounds from the spirooxindole tetrahydropyran derivatives and related molecules were screened for inhibition of sterol O-acyltransferase (SOAT) isozymes SOAT1 and SOAT2. Three racemic derivatives inhibited the SOAT2 isozyme with three-fold or better selectivity for SOAT2 than for SOAT1. The enantiomerically enriched forms of the most efficient racemic inhibitor of SOAT2 were further evaluated; one enantiomer inhibited SOAT2 with an IC50 of 1.5μM and was 10-fold more selective for SOAT2 than SOAT1.
CiteXplore: 27876317