Madaiah Malavalli, Prashanth Maralekere K, Revanasiddappa Hosakere D, Veeresh Bantal
Department of Chemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
Arch Pharm (Weinheim). 2014 May;347(5):370-80. doi: 10.1002/ardp.201300289. Epub 2014 Jan 21.
A series of novel 1'-[2-(difluoromethoxy)benzyl]-2'H,5'H-spiro[8-azabicyclo[3.2.1]octane-3,4'-imidazolidine]-2',5'-dione substituted hydantoins (5-32) were synthesized using an appropriate synthetic route and characterized by elemental analysis and spectral data. The novel molecules were screened for anticonvulsant activity in mice by maximal electroshock (MES) and subcutaneous pentylenetetrazol (ScPTZ)-induced seizure tests. The neurotoxicity was assessed using the rotarod method. Compounds 9, 10, 18, 30, and 31 exhibited anticonvulsant potency against MES seizure and in the ScPTZ model, with lesser neurotoxicity. Some title compounds showed lesser central nervous system depression compared to phenytoin.
通过适当的合成路线合成了一系列新型的1'-[2-(二氟甲氧基)苄基]-2'H,5'H-螺[8-氮杂双环[3.2.1]辛烷-3,4'-咪唑烷]-2',5'-二酮取代乙内酰脲（5-32），并通过元素分析和光谱数据对其进行了表征。通过最大电休克（MES）和皮下注射戊四氮（ScPTZ）诱导的癫痫试验，在小鼠中筛选了这些新型分子的抗惊厥活性。使用转棒试验评估神经毒性。化合物9、10、18、30和31在MES癫痫模型和ScPTZ模型中表现出抗惊厥效力，且神经毒性较小。与苯妥英相比，一些标题化合物表现出较小的中枢神经系统抑制作用。
