Add time:09/02/2019         Source:sciencedirect.com

We describe a novel class of acidic mPGES-1 inhibitors with nanomolar enzymatic and human whole blood (HWB) potency. Rational design in conjunction with structure-based design led initially to the identification of anthranilic acid 5, an mPGES-1 inhibitor with micromolar HWB potency. Structural modifications of 5 improved HWB potency by over 1000×, reduced CYP2C9 single point inhibition, and improved rat clearance, which led to the selection of [(cyclopentyl)ethyl]benzoic acid compound 16 for clinical studies. Compound 16 showed an IC80 of 24 nM for inhibition of PGE2 formation in vitro in LPS-stimulated HWB. A single oral dose resulted in plasma concentrations of 16 that exceeded its HWB IC80 in both rat (5 mg/kg) and dog (3 mg/kg) for over twelve hours.

We also recommend Trading Suppliers and Manufacturers of ANTHRANILIC ACID, N-BOC-4-CHLORO (cas 136290-47-6). Pls Click Website Link as below: cas 136290-47-6 suppliers