Ergoline-Derived Inverse Agonists of the Human H3 Receptor for the Treatment of Narcolepsy

Ergoline derivative (6aR,9R)‐4‐(2‐(dimethylamino)ethyl)‐N‐phenyl‐9‐(pyrrolidine‐1‐carbonyl)‐6,6a,8,9‐tetrahydroindolo[4,3‐fg]quinoline‐7(4H)‐carboxamide ( 1 ), a CXCR3 antagonist, also inhibits human histamine H3 receptors (H3R) and represents a structurally novel H3R inverse agonist chemotype. It displays favorable pharmacokinetic and in vitro safety profiles, and served as a lead compound in a program to explore ergoline derivatives as...