Synthesis and biological assays of new H3-antagonists with imidazole and imidazoline polar groups
| Autor: | Vigilio Ballabeni, Valentina Zuliani, Marco Mor, Silvia Rivara, Mariannina Impicciatore, Federica Vacondio, Pier Vincenzo Plazzi, Elisabetta Barocelli, Claudia Silva, Giovanni Morini, Fabrizio Bordi |
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| Rok vydání: | 2000 |
| Předmět: |
chemistry.chemical_classification
Stereochemistry Guinea Pigs Histamine Antagonists Imidazoles Antagonist Brain Pharmaceutical Science Imidazoline receptor Ring (chemistry) Chemical synthesis Electric Stimulation Rats Radioligand Assay chemistry.chemical_compound Membrane chemistry Ileum Drug Discovery Animals Receptors Histamine H3 Imidazole Rats Wistar Histamine Alkyl |
| Zdroj: | Il Farmaco. 55:27-34 |
| ISSN: | 0014-827X |
| DOI: | 10.1016/s0014-827x(99)00115-9 |
| Popis: | New histamine H3-receptor antagonists were synthesised and tested on rat brain membranes and on electrically stimulated guinea-pig ileum. The new compounds have a central polar group represented by a 2-alkylimidazole or a 2-thioimidazoline nucleus. The effect of the polar group basicity on the optimal length of the alkyl chain, connecting this group to a 4(5)-imidazolyl ring, was investigated. The best affinity values, obtained by displacement of [3H]-RAMHA from rat brain, were obtained for the 2-alkylimidazole derivatives (2a-f) with tetramethylene chain (pKi 8.03-8.97), having an intermediate basicity between that of the previously reported 2-thioimidazoles (1a-i) and that of 2-alkylthioimidazolines (3a-h). In contrast, a general lowering of affinity (pKi 5.90-7.63) was observed for compounds of the last series (3a-h), with a complex dependence on the terminal lipophilic group and chain length. |
| Databáze: | OpenAIRE |
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