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ID: ALA1153136

Journal: Bioorg Med Chem Lett

Title: Novel benzoylpiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide and its plasma triglyceride-lowering effects in Zucker fatty rats.

Authors: Uto Y, Ogata T, Kiyotsuka Y, Ueno Y, Miyazawa Y, Kurata H, Deguchi T, Watanabe N, Konishi M, Okuyama R, Kurikawa N, Takagi T, Wakimoto S, Ohsumi J.

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).

CiteXplore: 19926281

DOI: 10.1016/j.bmcl.2009.10.101