Synthesis and anticonvulsant activity of 4-(2-(2,6-dimethylphenylamino)-2-oxoethylamino)-N-(substituted)butanamides: a pharmacophoric hybrid approach
| Autor: | Jegadeesan Vaigunda Ragavendran, Puppala Sahitya, Perumal Yogeeswari, Velagaleti Ranganadh, Dharmarajan Sriram |
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| Rok vydání: | 2007 |
| Předmět: |
Stereochemistry
medicine.drug_class medicine.medical_treatment Chemistry Pharmaceutical Clinical Biochemistry Pharmaceutical Science Carboxamide Motor Activity Biochemistry Chemical synthesis chemistry.chemical_compound Mice Structure-Activity Relationship Seizures Drug Discovery medicine Animals Molecular Biology gamma-Aminobutyric Acid Neurons Seizure threshold Ethanol Molecular Structure Organic Chemistry Biological activity Anticonvulsant chemistry Models Chemical Blood-Brain Barrier Drug Design Lipophilicity Molecular Medicine Anticonvulsants Pharmacophore Picrotoxin |
| Zdroj: | Bioorganicmedicinal chemistry letters. 17(13) |
| ISSN: | 0960-894X |
| Popis: | A series of pharmacophoric hybrids of ameltolide-γ-aminobutyric acid (GABA)-amides was designed, synthesized, and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (ip) maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ), and subcutaneous picrotoxin (scPIC)-induced seizure threshold tests. All the compounds had improved lipophilicity and the pharmacological activity profile confirmed their blood–brain barrier penetration. The titled compounds showed promising activity in scPIC screen indicating the involvement of GABA-mediation. Compound 4-(2-(2,6-dimethylaminophenylamino)-2-oxoethylamino)- N -(2,6-dimethylphenyl) butanamide ( 7 ) emerged as the most potent derivative effective in all the three animal models of seizure with no neurotoxicity at the anticonvulsant dose. |
| Databáze: | OpenAIRE |
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