Synthesis and anticonvulsant properties of 1-(amino-N-arylmethanethio)-3-(1-substituted benzyl-2, 3-dioxoindolin-5-yl) urea derivatives

被引：32
作者：
Siddiqui, Nadeem [1 ]
Alam, M. Shamsher [1 ]
Stables, James P. [2 ]
机构：
[1] Hamdard Univ, Dept Pharmaceut Chem, Fac Pharm, New Delhi 110062, India
[2] Natl Inst Neurol Disorders & Stroke, Epilepsy Branch, NIH, Rockville, MD 20892 USA
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 06期
关键词：
Isatin; Anticonvulsants; Neurotoxicity; EARLY IDENTIFICATION; ISATIN; INHIBITORS; OXINDOLES; TOXICITY; DESIGN;
D O I：
10.1016/j.ejmech.2011.03.004
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Various 1-(amino-N-arylmethanethio)-3-(1-substituted benzyl-2, 3-dioxoindolin-5-yl) urea (5a-p) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Their in vivo anticonvulsant screenings were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Compound 5f was found active in MES screening while compounds 5h, 5i, 5k and 5i showed significant anticonvulsant activity in both the screenings and were devoid of any neurotoxicity. Compound 5h and 51 showed marked protection at 300 mg/kg against MES and scPTZ screening. Compound 5i also showed protection against MES screening at the dose of 100 mg/kg. In 6 Hz screening these two compounds showed significant protection and emerged as lead compounds for future investigations. (C) 2011 Elsevier Masson SAS. All rights reserved.
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页码：2236 / 2242
页数：7
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