Frédéric Donche

TL;DR: A novel series of quinoline isoxazole BET family bromodomain inhibitors shows good oral bioavailability in both the rat and minipig as well as demonstrating efficient suppression of bacterial induced inflammation and sepsis in a murine in vivo endotoxaemia model.

TL;DR: The discovery, synthesis and biological evaluation of a novel series of 7-isoxazoloquinolines is described and several analogs are shown to increase ApoA1 expression within the nanomolar range in the human hepatitis cell line HepG2.

TL;DR: The design of potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitors starting from a high-throughput screen and the lead-optimization of this series from a lead with minimal rat oral exposure to the identification of dihydroberazole 77 with good pharmacokinetic profiles in multiple species are reported on.

TL;DR: It is demonstrated that for this series of inhibitors, a reduction of systemic exposure is not sufficient to circumvent cataract liabilities.

TL;DR: The discovery of pyrrolopyridone derivatives as AMPK direct activators is reported and the synthesis and structure-activity relationships of the series are illustrated as well as some pharmacokinetic results.