Novel and highly potent histamine H3 receptor ligands. Part 3: an alcohol function to improve the pharmacokinetic profile
| Autor: | Marc Capet, Philippe Robert, Thierry Calmels, Jean-Charles Schwartz, Jeanne-Marie Lecomte, Olivia Poupardin-Olivier, Isabelle Berrebi-Bertrand, Olivier Labeeuw, Xavier Ligneau, Nicolas Levoin |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Drug Inverse Agonism Clinical Biochemistry Cyclohexanol Pharmaceutical Science Alcohol Pharmacology Ligands Biochemistry chemistry.chemical_compound Mice In vivo Drug Discovery Animals Humans Receptors Histamine H3 Receptor Molecular Biology Binding Sites Ethanol Organic Chemistry Cyclohexanols Recombinant Proteins Protein Structure Tertiary Molecular Docking Simulation chemistry Molecular Medicine Pharmacophore Histamine H3 receptor Histamine Function (biology) Half-Life Histamine H3 Antagonists Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry letters. 23(9) |
| ISSN: | 1464-3405 |
| Popis: | Synthesis and biological evaluation of potent histamine H3 receptor antagonists incorporating a hydroxyl function are described. Compounds in this series exhibited nanomolar binding affinities for human receptor, illustrating a new possible component for the H3 pharmacophore. As demonstrated with compound BP1.4160 (cyclohexanol 19), the introduction of an alcohol function counter-intuitively allowed to reach high in vivo efficiency and favorable pharmacokinetic profile with reduced half-life. |
| Databáze: | OpenAIRE |
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