Synthesis and anticonvulsant activity of 4-(2-(2,6-dimethylphenylamino)-2-oxoethylamino)-N-(substituted)butanamides: A pharmacophoric hybrid approach
详细信息 查看全文
- 作者：Perumal Yogeeswari ; Dharmarajan Sriram ; Puppala Sahitya ; Jegadeesan Vaigunda Ragavendran ; Velagaleti Ranganadh
- 关键词：Anticonvulsant ; GABA ; Ameltolide ; Pharmacophore ; 2 ; 6-Dimethylphenyl
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 出版时间：1 July 2007
- 年：2007
- 卷：17
- 期：13
- 页码：3712-3715
- 全文大小：124 K
文摘
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.