Structural–activity relationship study on C-4 carbon atom of the CB1 antagonist SR141716: synthesis and pharmacological evaluation of 1,2,4-triazole-3-carboxamides
| Autor: | Alberto Dordal, Nadine Jagerovic, Pilar Goya, María Isabel Martín, Angela Alsasua, Laura Hernandez-Folgado, Jordi Frigola, Jörg Holenz, Ibon Alkorta, María Teresa Dannert, Maria Rosa Cuberes |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cannabinoid receptor Molecular model Stereochemistry medicine.drug_class medicine.medical_treatment Carboxamide Pyrazole Chemical synthesis Mice Structure-Activity Relationship chemistry.chemical_compound Vas Deferens Piperidines Receptor Cannabinoid CB1 Drug Discovery medicine Animals Binding site Pharmacology Binding Sites Organic Chemistry 1 2 4-Triazole General Medicine Triazoles Cyclohexanols chemistry Pyrazoles lipids (amino acids peptides and proteins) Cannabinoid Rimonabant |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2005.06.012 |
| Popis: | A series of 1,2,4-triazole-3-carboxamides has been prepared from alkyl-1,2,4-triazole-3-carboxylates under mild conditions. The ability of these triazoles to displace [3H]-CP55940 from CB1 cannabinoid receptor was measured. However, they showed only poor to moderate binding affinities, indicating that substitution of the C-4 pyrazole atom of the CB 1 reference compound SR141716 by a nitrogen atom results in loss of affinity. Further investigations for functionality indicated that the compound 6a exhibited significant cannabinoid antagonistic properties in the mouse vas deferens functional assay. This leads us to the conclusion that 6a binds at a different CB1 binding site or at a new cannabinoid receptor subtype. © 2005 Elsevier SAS. All rights reserved. |
| Databáze: | OpenAIRE |
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