1414796-01-2

Upstream product

• 17529-16-7 6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalene-2-acetic acid 
• 13587-70-7 2-(6-methoxy-1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene)acetic acid 
• 1414797-84-4 2-(6-hydroxy-2-methyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid 
• 1078-19-9 6-methoxy-3,4-dihydro-1(2H)-naphthalenone 
• 1414797-83-3 ethyl 2-(6-methoxy-2-methyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)acetate 
• 50558-96-8 6-methoxy-1,2,3,4-tetrahydro-1-oxonaphthalene-2-acetic acid, ethyl ester 

Relevant academic research and scientific papers

Discovery of Tetralones as Potent and Selective Inhibitors of Acyl-CoA:Diacylglycerol Acyltransferase 1

Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) plays an important role in triglyceride synthesis and is a target of interest for the treatment of metabolic disorders. Herein we describe the structure-activity relationship of a novel tetralone series of DGAT1 inhibitors and our strategies for overcoming genotoxic liability of the anilines embedded in the chemical structures, leading to the discovery of a candidate compound, (S)-2-(6-(5-(3-(3,4-difluorophenyl)ureido)pyrazin-2-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid (GSK2973980A, 26d). Compound 26d is a potent and selective DGAT1 inhibitor with excellent DMPK profiles and in vivo efficacy in a postprandial lipid excursion model in mice. Based on the overall biological and developability profiles and acceptable safety profiles in the 7-day toxicity studies in rats and dogs, compound 26d was selected as a candidate compound for further development in the treatment of metabolic disorders.

Novel Compounds as Diacylglycerol Acyltransferase Inhibitors

This invention relates to novel compounds which are inhibitors of acyl coenzymeA: diacylglycerol acyltransferase 1 (DGAT-1), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of diseases related to DGAT-1 dysfunction or where modulation of DGAT-1 activity may have therapeutic benefit including but not limited to obesity, obesity related disorders, hypertriglyceridemia, hyperlipoproteinemia, chylomicronemia, dyslipidemia, non-alcoholic steatohepatitis, diabetes, insulin resistance, metabolic syndrome, hepatitis C virus infection and acne or other skin disorders.