Synthesis and anticonvulsant activity of enaminones
| Autor: | Jesse M. Nicholson, Christine N. Hinko, Hyejung Chang, K. R. Scott, Dianna Mulzac, Jacqueline A. Moore, Ivan O. Edafiogho |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Phenethylamine medicine.medical_treatment Drug Evaluation Preclinical Pharmacology Pyrrolidine chemistry.chemical_compound Mice Structure-Activity Relationship Seizures Morpholine Drug Discovery medicine Kindling Neurologic Structure–activity relationship Animals Amines Neurotoxicity Biological activity medicine.disease Electric Stimulation Rats Anticonvulsant chemistry Toxicity Molecular Medicine Anticonvulsants |
| Zdroj: | Journal of medicinal chemistry. 35(15) |
| ISSN: | 0022-2623 |
| Popis: | A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate++ + (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of greater than 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|