Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi 110062, India.
Eur J Med Chem. 2011 Jun;46(6):2236-42. doi: 10.1016/j.ejmech.2011.03.004. Epub 2011 Mar 10.
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 5l showed significant anticonvulsant activity in both the screenings and were devoid of any neurotoxicity. Compound 5h and 5i 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.
设计了各种 1-（氨基-N-芳基甲硫基）-3-（1-取代苄基-2,3-二氧代吲哚啉-5-基）脲（5a-p），这些化合物的设计考虑了抗惊厥活性的药效团模型中提出的结构要求。通过两种最常用的癫痫发作模型（最大电休克发作（MES）和皮下戊四氮（scPTZ））进行了它们的体内抗惊厥筛选。化合物 5f 在 MES 筛选中表现出活性，而化合物 5h、5i、5k 和 5l 在两种筛选中均表现出显著的抗惊厥活性，且没有任何神经毒性。化合物 5h 和 5i 在 300 mg/kg 剂量下对 MES 和 scPTZ 筛选均表现出明显的保护作用。化合物 5i 还在 100 mg/kg 剂量下对 MES 筛选表现出保护作用。在 6 Hz 筛选中，这两种化合物均表现出显著的保护作用，成为未来研究的先导化合物。
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