Add time:08/07/2019         Source:sciencedirect.com

MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target for the drug treatment of obesity, diabetes, and other disease. We describe our exploration and structure–activity relationship (SAR) study of 2,3-dihydro-1H-isoindole-5-sulfonamide derivatives. In this study, we identified 29 as an orally available inhibitor of MGAT2 through optimization especially in terms of solubility. This compound exhibited moderate potency in the enzyme inhibitory assay (IC50 = 1522 nM) and significant suppression of fat absorption (57% inhibition) in mice oral lipid tolerance test.

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