Development of Novel Benzomorpholine Class of Diacylglycerol Acyltransferase I Inhibitors
Year: 2014
Type: article
Abstract: Diacylglycerol acyltransferase 1 (DGAT1) presents itself as a potential therapeutic target for obesity and diabetes for its important role in triglyceride biosynthesis. Herein we report the rational design of a novel class of DGAT1 inhibitors featuring a benzomorpholine core (23n). SAR exploration yielded compounds with good potency and selectivity as well as reasonable physical and pharmacokinetic properties. This class of DGAT1 inhibitors was tested in rodent models to evaluate DGAT1 inhibition as a novel approach for the treatment of metabolic diseases. Compound 23n conferred weight loss and a reduction in liver triglycerides when dosed chronically in mice with diet-induced obesity and depleted serum triglycerides following a lipid challenge.
Source: ACS Medicinal Chemistry Letters
DOI: 10.1021/ml400527n
Authors: Gang Zhou, Nicolas Zorn, Pauline Ting, Robert Aslanian, Mingxiang Lin, John Cook, Jean Lachowicz, Albert Lin, Michelle Smith, Joyce Hwa, Margaret van Heek, Scott Walker
Institution: Merck & Co., Inc., Rahway, NJ, USA (United States)
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: green
Funder: AstraZeneca
OpenAlex ID: W2332504635