The discovery of quinoline based single-ligand human H 1 and H 3 receptor antagonists
| Autor: | Steven Philip Keeling, Nigel J. Parr, Simon Teanby Hodgson, Ashley Paul Hancock, Duncan S. Holmes, Panayiotis A. Procopiou, James E. Rowedder, Brian Edgar Looker, Robert J. Slack, Paul Martin Gore, Rachael A. Ancliff |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stereochemistry Clinical Biochemistry hERG Pharmaceutical Science Histamine Receptor Antagonists Pharmacology 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Drug Discovery medicine Potency Receptor Molecular Biology biology Chemistry Organic Chemistry Quinoline Azelastine 0104 chemical sciences 010404 medicinal & biomolecular chemistry 030104 developmental biology biology.protein Molecular Medicine Nasal administration medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 26:5855-5859 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2016.11.022 |
| Popis: | A novel series of potent quinoline-based human H1 and H3 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 H1 potency (pA2 8.8 vs 9.7 for the clinical goldstandard azelastine), and H3 potency (pKi 9.1vs 6.8 for azelastine), better selectivity over α1A, α1B and hERG, similar duration of action, making 18b a good back-up compound to our previous candidate, but with a more desirable profile. |
| Databáze: | OpenAIRE |
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