4-Phenoxypiperidines: Potent, Conformationally Restricted, Non-Imidazole Histamine H3 Antagonists
| Autor: | Curt A. Dvorak, Craig W. Berridge, Timothy W. Lovenberg, Sandy J. Wilson, Jamin D. Boggs, Wei Xiao, Ann J. Barbier, Richard Apodaca, Nicholas I. Carruthers |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Stereochemistry medicine.drug_class Histamine Antagonists Molecular Conformation Chemical synthesis Cell Line Rats Sprague-Dawley Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Piperidines In vivo Drug Discovery medicine Animals Humans Receptors Histamine H3 Moiety Imidazole Structure–activity relationship Wakefulness Behavior Animal Electromyography Antagonist Brain Electroencephalography Receptor antagonist Rats chemistry Autoradiography Molecular Medicine Sleep Histamine |
| Zdroj: | Journal of Medicinal Chemistry. 48:2229-2238 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Two new series of 4-(1-alkyl-piperidin-4-yloxy)-benzonitriles and 4-(1-isopropyl-piperidin-4-yloxy)-benzylamines have been prepared. In vitro activity was determined at the recombinant human H(3) receptor and several members of these new series were found to be potent H(3) antagonists. The present compounds contain a 4-phenoxypiperidine core, which behaves as a conformationally restricted version of the 3-amino-1-propanol moiety common to the many previously described non-imidazole histamine H(3) ligands. One selected member of the new series, 4-[4-(1-isopropyl-piperidin-4-yloxy)-benzyl]-morpholine (13g), was found to be a potent, highly selective H(3) receptor antagonist with in vivo efficacy in a rat EEG model of wakefulness at doses as low as 1 mg/kg sc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|