1477523-91-3

Upstream product

• 41841-16-1 (4-bromo-phenyl)-acetic acid methyl ester 
• 1384265-30-8 methyl 1-(4-bromophenyl)-4-oxocyclohexane-1-carboxylate 
• 1477524-07-4 methyl 2-(4-(4-bromophenyl)-4-(hydroxymethyl)cyclohexylidene)acetate 
• 1477524-06-3 4-(4-bromophenyl)-4-(hydroxymethyl)cyclohexan-1-one 
• 1477524-05-2 (8-(4-bromophenyl)-1,4-dioxaspiro[4.5]decan-8-yl)methanol 
• 1477524-35-8 methyl 2-(4-(4'-(2-ethyl-4-methyloxazole-5-carboxamido)-[1,1'-biphenyl]-4-yl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate 
• 1477524-08-5 methyl 2-(4-(4-bromophenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate 
• 1477524-34-7 2-ethyl-4-methyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazole-5-carboxamide 
• 113366-51-1 2-ethyl-4-methyl-1,3-oxazole-5-carboxylic acid 
• 1477524-04-1 methyl 8-(4-bromophenyl)-1,4-dioxaspiro[4.5]decane-8-carboxylate 
• 214360-73-3 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)aniline 

Relevant academic research and scientific papers

Successful strategies for mitigation of a preclinical signal for phototoxicity in a dgat1 inhibitor

Diacylglycerol O-acyltransferase 1 (DGAT1) inhibitor Pradigastat (1) was shown to be effective at decreasing postprandial triglyceride levels in a patient population with familial chylomicronemia syndrome (FCS). Although pradigastat does not cause photosensitization in humans at the high clinical dose of 40 mg, a positive signal was observed in preclinical models of phototoxicity. Herein, we describe a preclinical phototoxicity mitigation strategy for diarylamine containing molecules utilizing the introduction of an amide or suitable heterocyclic function. This strategy led to the development of two second-generation compounds with low risk of phototoxicity, disparate exposure profiles, and comparable efficacy to 1 in a rodent lipid bolus model for post-prandial plasma triglycerides.

CYCLIC BRIDGEHEAD ETHER DGAT1 INHIBITORS

The invention relates to compounds of formula (I): useful for treating disorders mediated by acyl coA-diacylglycerol acyl transferase 1 (DGAT1), e.g. metabolic disorders. The invention also provides methods of treating such disorders, and compounds and compositions etc. for their treatment.