Heterocyclic replacement of the central phenyl core of diamine-based histamine H3 receptor antagonists
| Autor: | Timothy W. Lovenberg, Lisa Dvorak, Jamin D. Boggs, Brian Lord, Curt Mazur, Swanson Devin M, Pascal Bonaventure, Richard Apodaca, Chandra R. Shah, Kirsten L. Morton, Ann J. Barbier, Mark A. Feinstein, Sandy J. Wilson, Nicholas I. Carruthers, Wei Xiao |
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| Rok vydání: | 2009 |
| Předmět: |
Pharmacology
Pyrazine Stereochemistry Organic Chemistry General Medicine Diamines Cell Line Rats Rats Sprague-Dawley chemistry.chemical_compound chemistry Blood-Brain Barrier Drug Discovery Thiophene Animals Humans Receptors Histamine H3 Histamine H3 receptor Isoxazole Thiazole H3 receptor antagonist Histamine H3 Antagonists Protein Binding Pyrrole Oxazole |
| Zdroj: | European Journal of Medicinal Chemistry. 44:4413-4425 |
| ISSN: | 0223-5234 |
| Popis: | A series of small molecules consisting of a heterocyclic core flanked by two basic functionalities were synthesized and screened for in vitro affinity at the human histamine H 3 receptor (hH 3 R). Nine of the twenty-eight compounds tested were found to possess a hH 3 R K i of less than 5 nM and consisted of a diverse range of central hetero-aromatic linkers (pyridine, pyrazine, oxazole, isoxazole, thiazole, furan, thiophene, and pyrrole). One member of this series, (4-isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanone ( 37 ), was found to be a high affinity, selective antagonist that crosses the blood-brain barrier and occupies H 3 receptors after oral administration in the rat. |
| Databáze: | OpenAIRE |
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