Article ID Journal Published Year Pages File Type
1372489 Bioorganic & Medicinal Chemistry Letters 2010 5 Pages PDF
Abstract

Starting from a known piperazine-based SCD-1 inhibitor, we obtained more potent benzoylpiperidine analogs. Optimization of the structure of the benzoylpiperidine-based SCD-1 inhibitors resulted in the identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-yl-ethyl)amide (24) which showed strong inhibitory activity against both human and murine SCD-1. In addition, this compound exhibited good oral bioavailability and demonstrated plasma triglyceride lowering effects in Zucker fatty rats in a dose-dependent manner after a 7-day oral administration (qd).

Graphical abstractOptimization of the structure of benzoylpiperidine-based stearoyl-CoA desaturase-1 inhibitors resulted in the identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide which demonstrated plasma triglyceride-lowering effects in Zucker fatty rats in a dose-dependent manner after a 7-day administration (qd).Figure optionsDownload full-size imageDownload as PowerPoint slide

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Physical Sciences and Engineering Chemistry Organic Chemistry
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