The discovery of quinoline based single-ligand human H1 and H3 receptor antagonists

Abstract A novel series of potent quinoline-based human H 1 and H 3 bivalent histamine receptor antagonists, suitable for intranasal administration for the potential treatment of allergic rhinitis associated nasal congestion, were identified. Compound 18b had slightly lower H 1 potency (pA 2 8.8 vs 9.7 for the clinical goldstandard azelastine), and H 3 potency (p K i 9.1 vs 6.8 for azelastine), better selectivity over α 1A , α 1B and hERG, similar duration of action, making 18b a good back-up compound to our previous candidate, but with a more desirable profile.