3-Aryl-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones: Tricyclic Heteroaromatic Derivatives as a New Class of Benzodiazepine Receptor Ligands
| Autor: | Ettore Novellino, F. Da Settimo, Letizia Trincavelli, G. Primofiore, Anna Maria Marini, Giovanni Greco, Marco Gesi, Claudia Martini, Sabrina Taliani, C. La Motta |
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| Přispěvatelé: | Primofiore, G., DA SETTIMO, F., Taliani, S., Marini, A. M., LA MOTTA, C., Novellino, Ettore, Greco, Giovanni, Gesi, M., Trincavelli, L., Martini, C. |
| Rok vydání: | 1999 |
| Předmět: |
Flumazenil
Models Molecular Stereochemistry Convulsants In Vitro Techniques Ligands Partial agonist Chemical synthesis Mice Radioligand Assay chemistry.chemical_compound Drug Discovery medicine Animals Inverse agonist GABA Modulators chemistry.chemical_classification Diazepam Membranes Chemistry Aryl Brain Receptors GABA-A Tautomer Lactam Molecular Medicine Anticonvulsants Benzimidazoles Cattle Tricyclic medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 43:96-102 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm991131h |
| Popis: | A series of 3-substituted [1,2,4]triazino[4,3-c]benzimidazoles V were prepared and tested at the central benzodiazepine receptor (BzR). These compounds were designed as rigid analogues of the previously described N-benzylindolylglyoxylylamide derivatives IV. The title compounds V showed an affinity which depended directly on the presence of the N(10)-H group and an aromatic ring at position 3. Some of them elicited a 2- or 3-fold higher affinity with respect to that of the indolylglyoxylylamide derivatives IV (R = H). The GABA ratio and [(35)S]-tert-butylcyclophosphorothionate binding data revealed an efficacy profile of partial inverse agonists/antagonists for compounds 1c,e,f,j,k, and of a partial agonist for 2c. This last compound proved to be effective in antagonizing pentylenetetrazole-induced seizures in mice. Attempts were made to interpret the structure-affinity relationships of compounds V in the light of possible tautomeric equilibria involving the ligands. |
| Databáze: | OpenAIRE |
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