2-Phenyl-3H-imidazo[4,5-b]pyridine-3-acetamides as nonbenzodiazepine anticonvulsants and anxiolytics
| Autor: | L. M. Moses, B. F. Kilpatrick, Taylor Cr, Lo Ys, Johnson Dn, W. B. Kinnier, Tomczuk Be, D. B. Sutherland |
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| Rok vydání: | 1991 |
| Předmět: |
Agonist
Pyridines medicine.drug_class medicine.medical_treatment Carboxamide Anxiety Pharmacology Binding Competitive Anxiolytic Benzodiazepines Mice Seizures Drug Discovery medicine Animals Potency gamma-Aminobutyric Acid Cerebral Cortex Mice Inbred ICR Molecular Structure Chemistry Imidazoles Neurotoxicity Biological activity Receptors GABA-A medicine.disease Rats Anticonvulsant Anti-Anxiety Agents Molecular Medicine Anticonvulsants Diazepam medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 34:2993-3006 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A series of 2-phenyl-3H-imidazo[4,5-b]pyridine-3-acetamides were designed and synthesized as non-benzodiazepine anxiolytics based on a molecular disconnection of a typical 1,4-benzodiazepine (BZD). A number of these compounds showed submicromolar potency in a [3H]benzodiazepine binding assay in vitro and good potency in protecting rodents against pentylenetetrazole-induced seizures. Compound 84 appears to be a selective anticonvulsant (pentylenetetrazole) agent when tested against a profile of chemically and electrically induced seizures in mice. In addition, compound 148 appears to be a selective anxiolytic/hypnotic agent on the basis of biochemical and pharmacological characterization. It appears to be a full BZD agonist as assessed by GABA shift ratio and to be effective in punishment and nonpunishment animal models of anxiety. In addition, it shows a lower side-effect profile than diazepam as assessed by rotorod neurotoxicity and potentiation of ethanol-induced sleep time in mice. The chemistry and structure-activity relationships of this series is discussed. |
| Databáze: | OpenAIRE |
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