Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones
| Autor: | P. S. Loo, James L. Hyun, Debra A. Bennett, Francis John E, D. Wilson, Robert Neale, Caryl L. Amrick, Deborah Murphy, Stephen L. Rovinski |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
medicine.drug_class
Stereochemistry Alcohol Pyrimidinones Anxiolytic Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Alicyclic compound Drug Discovery medicine Animals chemistry.chemical_classification Benzodiazepine Ethanol Chemistry CGS-9896 Biological activity Triazoles Rats Aggression Anti-Anxiety Agents Conditioning Operant Molecular Medicine Diazepam medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 34:2899-2906 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00113a032 |
| Popis: | Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin- 5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e] [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described. |
| Databáze: | OpenAIRE |
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