Aggarwal Navneet, Mishra Pradeep, Nagori Badri Prakash, Aggarwal Ruchi, Jain Jainendra
Lachoo Memorial College of Science and Technology, Pharmacy Wing, Jodhpur, Rajasthan, India.
Cent Nerv Syst Agents Med Chem. 2009 Dec;9(4):295-9. doi: 10.2174/187152409789630442.
A series of 4-aryl substituted semicarbazones of pyridyl carbaldehyde and pyridyl methyl ketone were designed and synthesized to meet the structural requirements essential for anticonvulsant activity. The structure of synthesized compounds were confirmed by IR spectroscopy, PMR spectroscopy and nitrogen estimation. All the compounds were evaluated for anticonvulsant activity and neurotoxicity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Majority of compounds exhibited significant anticonvulsant activity after intraperitoneal administration. The results obtained showed that 85.7 % of the compounds afforded protection in the MES test and 64.2 % of the total compounds afforded protection in ScPTZ test. Some of them also showed good activity after oral administration. In this study (Methyl-4- pyridyl) ketone -N(4)- (p- chloro phenyl) substituted semicarbazone emerged as most active derivative showing activity at 100 mg/kg in both the test with prolonged duration of action. In the present study semicarbazones of pyridyl containing carbonyl compounds emerges as the lead molecule, showing broad spectrum of activity with low neurotoxicity and prolong duration of action on oral administration. Thus these may be utilized for the future development of novel anticonvulsants with broad spectrum of anticonvulsant activity.
设计并合成了一系列吡啶甲醛和吡啶甲基酮的4-芳基取代氨基脲，以满足抗惊厥活性所必需的结构要求。通过红外光谱、核磁共振氢谱和氮含量测定对合成化合物的结构进行了确认。对所有化合物进行了抗惊厥活性和神经毒性评估。通过最大电休克（MES）和皮下注射戊四氮（ScMet）诱导惊厥方法对小鼠腹腔注射后测定抗惊厥活性，并通过转杆试验测定最小运动损伤。大多数化合物腹腔注射后表现出显著的抗惊厥活性。所得结果表明，85.7%的化合物在MES试验中提供了保护作用，64.2%的化合物在ScPTZ试验中提供了保护作用。其中一些化合物口服后也表现出良好的活性。在本研究中，（甲基-4-吡啶基）酮-N（4）-（对氯苯基）取代氨基脲成为最具活性的衍生物，在两种试验中100mg/kg剂量时均表现出活性，且作用持续时间延长。在本研究中，含吡啶羰基化合物的氨基脲成为先导分子，显示出广谱活性，神经毒性低，口服作用持续时间延长。因此，这些化合物可用于未来开发具有广谱抗惊厥活性的新型抗惊厥药物。
