Medicinal Chemistry Division, F/o Pharmacy, Jamia Hamdard, New Delhi, India.
Chem Biol Drug Des. 2012 Jan;79(1):104-11. doi: 10.1111/j.1747-0285.2011.01255.x. Epub 2011 Nov 18.
A series of quinoline-incorporated substituted thiadiazole were designed and synthesized using appropriate synthetic route keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant and CNS activities. After intraperitoneal injection to mice, some synthesized derivatives were examined in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPTZ)-induced seizure and neurotoxicity screens. Those found potent were also evaluated for behavioural impairment and depression activity. Among the compounds tested, 6d and 6e showed protection from seizures in both the animal models at dose level of 30 mg/kg while 7f showed protection against both models at 100 mg/kg dose level. These compounds exhibited lesser CNS depression and neurotoxicity compared with clinically effective drug.
设计并合成了一系列含有喹啉的取代噻二唑，采用适当的合成路线，以满足药效团的结构要求，并对其进行了抗惊厥和中枢神经系统活性评价。在腹腔注射给药后，对部分合成衍生物进行了最大电休克惊厥（MES）和皮下戊四氮（scPTZ）诱导惊厥及神经毒性筛选。在测试的化合物中，化合物 6d 和 6e 在 30mg/kg 剂量水平下对两种动物模型均表现出了保护作用，而化合物 7f 在 100mg/kg 剂量水平下对两种模型均表现出了保护作用。与临床有效药物相比，这些化合物表现出较小的中枢神经系统抑制和神经毒性。
