Influence of imidazole replacement in different structural classes of histamine H3-receptor antagonists
| Autor: | Walter Schunack, C. Robin Ganellin, Xavier Ligneau, Holger Stark, Jean-Charles Schwartz, Fabien Leurquin, Galina Meier, Joachim Apelt, Sven Graßmann, Ulrich Reichert, Sigurd Elz |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Clobenpropit
Stereochemistry Guinea Pigs Histamine Antagonists Pharmaceutical Science Ether In Vitro Techniques Mice Structure-Activity Relationship chemistry.chemical_compound Cytochrome P-450 Enzyme System Ileum Ciproxifan medicine Animals Receptors Histamine H3 Moiety Imidazole Cerebral Cortex Thioperamide Imidazoles Muscle Smooth Rats chemistry Indicators and Reagents Piperidine Histamine H3 receptor Muscle Contraction Synaptosomes medicine.drug |
| Zdroj: | European Journal of Pharmaceutical Sciences. 13:249-259 |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/s0928-0987(01)00106-3 |
| Popis: | The reference compounds for histamine H(3)-receptor antagonists carry as a common feature an imidazole moiety substituted in the 4-position. Very recently novel ligands lacking an imidazole ring have been described possessing a N-containing non-aromatic heterocycle instead. In this study we investigated whether imidazole replacement, favourably by a piperidine moiety, is generally applicable to different structural classes of reference compounds, e.g., thioperamide, carboperamide, clobenpropit, FUB 181, ciproxifan, etc. While replacement led to a loss of affinity for many of the compounds, it was successfully applied to some ether derivatives. The piperidine analogues of FUB 181 and ciproxifan, 3-(4-chlorophenyl)propyl 3-piperidinopropyl ether hydrogen oxalate (6) and cyclopropyl 4-(3-piperidinopropyloxy)phenyl methanone hydrogen maleate (7), almost maintained in vitro affinities, pK(i) values of 7.8 and 8.4, respectively, and showed high potency in vivo after p.o. administration (ED(50) values of 1.6 and 0.18 mg/kg, respectively). |
| Databáze: | OpenAIRE |
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