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

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 (pK(i) 9.1 vs 6.8 for azelastine), better selectivity over alpha 1A, alpha 1B and hERG, similar duration of action, making 18b a good back-up compound to our previous candidate, but with a more desirable profile. (C) 2016 Elsevier Ltd. All rights reserved.