Structure–activity relationships (SAR) and structure–kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists III: The role of a hydrogen-bond acceptor in long receptor residence times

Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP2 Receptor Antagonist for Treatment of Asthma

“…This may be an explanation for the increased potency of 11 in the primary human eosinophil and Th2 cell assays and may positively impact clinical efficacy. Since this work was completed, the first reports of structure-kinetic relationships for DP 2 antagonists have appeared − together with characterization of a compound LAS191859 reported to have a half-life of 21 h based on GTPγS assay data and a duration of action apparently independent of plasma levels in a guinea pig mechanistic model of systemic eosinophilia . It is noteworthy that the kinetics in that work were determined at ambient temperature, whereas our studies were all undertaken at physiological temperature.…”