50558-96-8

Upstream product

• 13587-70-7 2-(6-methoxy-1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene)acetic acid 
• 1078-19-9 6-methoxy-3,4-dihydro-1(2H)-naphthalenone 
• 64-17-5 ethanol 
• 17529-16-7 6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalene-2-acetic acid 
• 105-36-2 ethyl bromoacetate 

Downstream Products

• 1609543-79-4 methyl 2-(6-(6-((3-chlorophenyl)amino)pyridazin-3-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetate 
• 1609543-68-1 (S)-methyl 2-(6-(6-((3-chlorophenyl)amino)pyridazin-3-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetate 
• 1609543-69-2 (R)-methyl 2-(6-(6-((3-chlorophenyl)amino)pyridazin-3-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetate 
• 1609543-60-3 (R)-ethyl 2-(6-(5-(4-chlorophenylamino)pyridin-2-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthal-en-2-yl)acetate 
• 1609543-61-4 (S)-ethyl 2-(6-(5-(4-chlorophenylamino)pyridin-2-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthal-en-2-yl)acetate 
• 1609543-76-1 ethyl 2-(6-(5-(4-chlorophenylamino)pyridin-2-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthal-en-2-yl)acetate 
• 1414796-51-2 2-[(2R)-2-ethyl-1-oxo-6-[4-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1,2,3,4-tetrahydronaphthalen-2-yl]acetic acid 

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.

NOVEL COMPOUNDS AS DIACYLGLYCEROL ACYLTRANSFERASE INHIBITORS

This invention relates to novel compounds which are inhibitors of acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT-1), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination with weight management therapies or other triglyceride lowering 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, genetic (Type 1, Type 5 hyperlipidemia) and acquired forms of hypertriglyceridemia or hyperlipoproteinemia- related disorders, caused by but not limited to lipodystrophy, hypothyroidism, medications (beta blockers, thiazides, estrogen, glucocorticoids, transplant) and other factors (pregnancy, alcohol intake), hyperlipoproteinemia, chylomicronemia, dyslipidemia, non-alcoholic steatohepatitis, diabetes, insulin resistance, metabolic syndrome, cardiovascular outcomes, angina, excess hair growth (including syndromes associated with hirsutism), nephrotic syndrome, fibrosis such as mycocardial, renal and liver fibrosis, hepatitis C virus infection and acne or other skin disorders.

NOVEL COMPOUNDS AS DIACYLGLYCEROL ACYLTRANSFERASE INHIBITORS

This invention relates to novel compounds which are inhibitors of acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT-1), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination with weight management therapies or other triglyceride lowering therapy for the prevention or treatment of diseases related to DGAT-1 dysfunction or where modulation of DGAT-1 activity may have therapeutic benefit.

Tetrahydronaphthalene-derived amino alcohols and amino ketones as potent and selective inhibitors of the delayed rectifier potassium current I Ks

Class III anti-arrhythmic drugs (e.g., dofetilide) prolong cardiac action potential duration (APD) by blocking the fast component of the delayed rectifier potassium current (IKr). The block of IKr can result in life threatening ventr

Synthesis, hypotensive and diuretic activities of several 3-hydrazino-5,6-dihydrobenzo[h]cinnolines. Part 10: Pyridazine derivatives

New 3-hydrazino-5,6-dihydrobenzo[h]cinnolines were prepared, and their effects on arterial pressure, diuresis and Na+ and K+ excretion in conscious normotensive rats were studied.

(Phenylmethoxy)phenyl Derivatives of Ω-Oxo- and Ω-Tetrazolylalkanoic Acids and Related Tetrazoles. Synthesis and Evaluation as Leukotriene D4 Receptor Antagonists

Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists.In the Ω--Ω-oxoalkanoic acid series, 5-phenyl>-3,3-dimethyl-5-oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pKB of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv).Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds.Inthe Ω-alkyl>tetrazolyl>alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat.The pKB value in the guinea pig ileum for 1--2H-tetrazol-5-yl>methyl>phenoxy>methyl>phenyl>ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv.The sodium salts of 8 (9) and 25(26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner.Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.

Leukotriene antagonists

This invention provides benzene derivatives which are leukotriene antagonists, formulations of those derivatives, and a method of using those derivatives for the treatment of conditions characterized by an excessive release of leukotrienes.