71510-77-5Relevant academic research and scientific papers
Anthranilic acid derivatives as novel ligands for farnesoid X receptor (FXR)
Merk, Daniel,Gabler, Matthias,Gomez, Roberto Carrasco,Flesch, Daniel,Hanke, Thomas,Kaiser, Astrid,Lamers, Christina,Werz, Oliver,Schneider, Gisbert,Schubert-Zsilavecz, Manfred
, p. 2447 - 2460 (2014/05/06)
Nuclear farnesoid X receptor (FXR) has important physiological roles in various metabolic pathways including bile acid, cholesterol and glucose homeostasis. The clinical use of known synthetic non-steroidal FXR ligands is restricted due to toxicity or poor bioavailability. Here we report the development, synthesis, in vitro activity and structure-activity relationship (SAR) of anthranilic acid derivatives as novel FXR ligands. Starting from a virtual screening hit we optimized the scaffold to a series of potent partial FXR agonists with appealing drug-like properties. The most potent derivative exhibited an EC50 value of 1.5 ± 0.2 μM and 37 ± 2% maximum relative FXR activation. We investigated its SAR regarding polar interactions with the receptor by generating derivatives and computational docking.
