Synthesis and anticonvulsant activities of 3,3-dialkyl- and 3-alkyl-3-benzyl-2-piperidinones (delta-valerolactams) and hexahydro-2H-azepin-2-ones (epsilon-caprolactams)
| Autor: | Steven M. Rothman, Douglas F. Covey, Karen E. Woodward, Tammy Latifi, P. Amruta Reddy, M. W. Hill, B. C. H. Hsiang, James A. Ferrendelli, Sarah M. McIlheran |
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| Rok vydání: | 1997 |
| Předmět: |
Stereochemistry
medicine.medical_treatment Chemical synthesis chemistry.chemical_compound Mice Drug Discovery Convulsion Pi medicine Animals Caprolactam ED50 Piperidones Valproic Acid Neurotoxicity medicine.disease Bridged Bicyclo Compounds Heterocyclic Rats Electrophysiology Anticonvulsant chemistry Phenobarbital Toxicity Lactam Molecular Medicine Ethosuximide Anticonvulsants medicine.symptom |
| Zdroj: | Journal of medicinal chemistry. 40(1) |
| ISSN: | 0022-2623 |
| Popis: | A series of 3-substituted 2-piperidinone (delta-valerolactam) and hexahydro-2H-azepin-2-one (epsilon-caprolactam) derivatives were prepared and evaluated as anticonvulsants in mice. In the 2-piperidinone series, 3,3-diethyl compound 7b is the most effective anticonvulsant against pentylenetetrazole-induced seizures (ED50, 37 mg/kg; PI (TD50/ED50), 4.46), and 3-benzyl compound 4c (ED50, 41 mg/kg; PI, 7.05) is the most effective anticonvulsant against seizures induced by maximal electroshock. By contrast, none of the epsilon-caprolactams tested had anticonvulsant effects below doses causing rotorod toxicity. log P values were correlated with neurotoxicity and [35S]TBPS displacement, but not with anticonvulsant activity. Electrophysiological evaluations of selected compounds from each series indicated that both the delta-valero-lactams and epsilon-caprolactams potentiated GABA-mediated chloride currents in rat hippocampal neurons. |
| Databáze: | OpenAIRE |
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