Discovery of cyclopropyl chromane-derived pyridopyrazine-1,6-dione γ-secretase modulators with robust central efficacy
Martin Pettersson, Douglas S. Johnson, Danica A. Rankic, Gregory W. Kauffman, Christopher W. am Ende, Todd W. Butler, Brian P. Boscoe, Edelweiss Evrard, Christopher J. Helal, John M. Humphrey, Antonia F. Stepan, Cory M. Stiff, Eddie Yang, Longfei Xie, Kelly R. Bales, Éva Hajós‐Korcsok, Stephen G. Jenkinson, Betty A. Pettersen, Leslie R. Pustilnik, David S. Ramirez · MedChemComm · 2016
in a rat time-course study. Application of the unpaced isolated heart Langendorff model enabled efficient differentiation of compounds with respect to cardiovascular safety, highlighting how minor structural changes can greatly impact the safety profile within a series of compounds.