Zhu Qifeng, Pan Yuanhu, Xu Zaixu, Li Ruimin, Qiu Guofu, Xu Wenjin, Ke Xianbing, Wu Lamei, Hu Xianming
State Key Laboratory of Virology, College of Pharmacy, Wuhan University, Wuhan 430072, China.
Eur J Med Chem. 2009 Jan;44(1):296-302. doi: 10.1016/j.ejmech.2008.02.024. Epub 2008 Mar 7.
Thirteen new 5-cyclopropanespirohydantoins with various N-3 substituents were synthesized and their pharmacological activity was determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by maximal electroshock seizure (MES) test and subcutaneous pentylenetetrazole (scPTZ) test models in mice. All compounds substituted with cyclopropyl group at fifth position of hydantoin ring showed better protection against MES test. Compounds 5b, 5d, 5e, 5g and 5j were found to be the most potent compounds of this series and compared with the reference drug phenytoin sodium in MES test. Compound 5j also showed equipotent activity with the standard drug sodium valproate at the doses of 20 and 40 mg kg(-1) in scPTZ test.
合成了13种具有不同N-3取代基的新型5-环丙基螺乙内酰脲，并测定了它们的药理活性，目的是更好地了解其抗惊厥活性的构效关系（SAR）。通过小鼠最大电休克惊厥（MES）试验和皮下注射戊四氮（scPTZ）试验模型评估了这些化合物的抗惊厥作用。在乙内酰脲环的第5位被环丙基取代的所有化合物在MES试验中表现出更好的保护作用。发现化合物5b、5d、5e、5g和5j是该系列中最有效的化合物，并在MES试验中与参比药物苯妥英钠进行了比较。在scPTZ试验中，化合物5j在20和40 mg kg(-1)剂量下也显示出与标准药物丙戊酸钠相当的活性。
