Bioorg Med Chem. 2010 Apr 1;18(7):2785-95. doi: 10.1016/j.bmc.2010.01.067. Epub 2010 Feb 4.

Novel acyl coenzyme A (CoA): diacylglycerol acyltransferase-1 inhibitors: synthesis and biological activities of diacylethylenediamine derivatives.

Nakada Y, Aicher TD, Le Huerou Y, Turner T, Pratt SA, Gonzales SS, Boyd SA, Miki H, Yamamoto T, Yamaguchi H, Kato K, Kitamura S.

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Medicinal Chemistry Research Laboratories, Takeda Pharmaceutical Company Ltd, 2-17-85, Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan. Nakada_Yoshihisa@takeda.co.jp

Abstract

A series of diacylethylenediamine derivatives were synthesized and evaluated for their inhibitory activity against DGAT-1 and pharmacokinetic profile to discover new small molecule DGAT-1 inhibitors. Among the compounds, N-[2-({[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}amino)ethyl]-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide 3x showed potent inhibitory activity and excellent PK profile. Oral administration of 3x to mice with dietary-induced obesity resulted in reduced body weight gain and white adipose tissue weight.

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Novel acyl coenzyme A (CoA): diacylglycerol acyltransferase-1 inhibitors: synthesis and biological activities of diacylethylenediamine derivatives.
Bioorg Med Chem. 2010 Apr 1 ;18(7):2785-95. doi: 10.1016/j.bmc.2010.01.067. Epub 2010 Feb 4 .

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