280776-44-5

Upstream product

• 164523-19-7 4,4,4-trifluorobutyl methanesulfonate 
• 123-08-0 4-hydroxy-benzaldehyde 
• 461-18-7 4,4,4-trifluorobutanol 

Downstream Products

• 1350642-15-7 (S)-4-(4-(4,4,4-trifluorobutoxy)benzyloxy)-N-((1R,2R)-1-hydroxy-1-phenylpropan-2-yl)-N,2-dimethylbutanamide 
• 1350642-09-9 (4-(4,4,4-trifluorobutoxy)phenyl)methanol 
• 1350642-10-2 1-(bromomethyl)-4-(4,4,4-trifluorobutoxy)benzene 
• 1350642-11-3 2-(4-(4,4,4-trifluorobutoxy)benzyloxy)ethanol 
• 1350642-13-5 1-((2-iodoethoxy)methyl)-4-(4,4,4-trifluorobutoxy)benzene 
• 1441067-31-7 C₃₀H₃₂F₆N₂O₃ 
• 1441057-15-3 (S)-3-(1H-tetrazol-5-yl)-4-p-tolyl-6-(4-(4,4,4-trifluorobutoxy)phenyl)-6-(trifluoromethyl)-5,6-dihydropyridin-2(1H)-one 

Relevant academic research and scientific papers

Screening Hit to Clinical Candidate: Discovery of BMS-963272, a Potent, Selective MGAT2 Inhibitor for the Treatment of Metabolic Disorders

MGAT2 inhibition is a potential therapeutic approach for the treatment of metabolic disorders. High-throughput screening of the BMS internal compound collection identified the aryl dihydropyridinone compound 1 (hMGAT2 IC50 = 175 nM) as a hit. Compound 1 had moderate potency against human MGAT2, was inactive vs mouse MGAT2 and had poor microsomal metabolic stability. A novel chemistry route was developed to synthesize aryl dihydropyridinone analogs to explore structure-activity relationship around this hit, leading to the discovery of potent and selective MGAT2 inhibitors 21f, 21s, and 28e that are stable to liver microsomal metabolism. After triaging out 21f due to its inferior in vivo potency, pharmacokinetics, and structure-based liabilities and tetrazole 28e due to its inferior channel liability profile, 21s (BMS-963272) was selected as the clinical candidate following demonstration of on-target weight loss efficacy in the diet-induced obese mouse model and an acceptable safety and tolerability profile in multiple preclinical species.

DIHYDROPYRIDINONE MGAT2 INHIBITORS

The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

Dihydropyridinone MGAT2 inhibitors

The present invention provides compounds of Formula (I): Formula (I) or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

DIHYDROPYRIDINONE MGAT2 INHIBITORS FOR USE IN THE TREATMENT OF METABOLIC DISORDERS

The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

TETRAZOLONE-SUBSTITUTED DIHYDROPYRIDINONE MGAT2 INHIBITORS

The present invention provides compounds of Formula (I): a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, a solvate thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

SUBSTITUTED PYRIDINONES AS MGAT2 INHIBITORS

The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, or a solvate thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

ARYL DIHYDROPYRIDINONE AND PIPERIDINONE MGAT2 INHIBITORS

The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

Synthesis and spectroscopic analysis of a stereoisomer library of the phytophthora mating hormone α1 and derived bis-Mosher esters

Fluorous mixture synthesis provided all eight diastereomers of the phytophthora hormone α1 with the R configuration at C11 as individual samples after demixing and detagging. The library of all possible bis-Mosher esters (16) was then made by esterification. Complete sets of 1H, 13C, and (for the Mosher esters) 19F NMR spectra were recorded, assigned, and compared with each other and with published spectra. Not all of the spectra are unique, and the 1H NMR spectra of the Mosher esters provided the most information. The previous assignment of the natural sample as an "all-R" stereoisomer mixed with its 3S-epimer was confirmed.