Design and synthesis of (5-amino-1, 2, 4-triazin-6-yl)(2-(benzo[d] isoxazol-3-yl) pyrrolidin-1-yl)methanone derivatives as sodium channel blocker and anticonvulsant agents
| Autor: | Sachin Malik, Suroor A. Khan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Phenytoin Stereochemistry medicine.medical_treatment Administration Oral Sodium Channels Mice Structure-Activity Relationship chemistry.chemical_compound Sodium channel blocker Seizures Drug Discovery Pi medicine Animals Structure–activity relationship Rats Wistar Pharmacology Electroshock Dose-Response Relationship Drug Molecular Structure Triazines Chemistry Benzisoxazole Isoxazoles General Medicine Rats Anticonvulsant Agent Anticonvulsant Mechanism of action Drug Design Anticonvulsants medicine.symptom Injections Intraperitoneal Sodium Channel Blockers medicine.drug |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry. 29:505-516 |
| ISSN: | 1475-6374 1475-6366 |
| DOI: | 10.3109/14756366.2013.815177 |
| Popis: | A series of novel (5-amino-3-substituted-1, 2, 4-triazin-6-yl) (2-(6-halo-substituted benzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5a-5r was synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and neurotoxicity was evaluated by the rotorod test. The MES test showed that (5-amino-3-phenyl-1, 2, 4-triazin-6-yl)(2-(6-fluorobenzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5c was found to be the most potent compound with ED50 value of 6.20 mg/kg (oral/rat) and a protective index (PI = ED50/TD50) value of >48.38, which was much higher than the PI of the reference drug phenytoin. To explain the possible mechanism of action of selected derivatives 5 b, 5 c, 5 i and 5 o, their influence on sodium channel was evaluated in vitro. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|