Rajak Harish, Thakur Bhupendra S, Kumar Pramod, Parmar Poonam, Sharma Prabodh Chander, Veerasamy Ravichandran, Kharya Murli Dhar
Medicinal Chemistry Research Laboratory, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur-495 009, India.
Acta Pol Pharm. 2012 Mar-Apr;69(2):253-61.
The incomplete seizure control with frequent adverse effects of current anticonvulsant drugs and the importance of semicarbazones, quinazolines and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore prompted us to carry out synthesis of three novel series of semicarbazones containing 1,3,4-thiadiazole and quinazoline ring. The chemical structures of these compounds were elucidated by elemental and spectral (IR, 1H NMR, 13C NMR and MS) analysis. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The rotorod test was conducted to evaluate neurotoxicity. The majority of the compounds were found active in the biological screening. The outcome of the present investigations proved that the four binding sites pharmacophore model is decisive for antiepileptic activity. An attempt has also been performed to establish structure-activity relationships among synthesized compounds.
当前抗惊厥药物频繁出现不良反应且癫痫控制不完全,以及氨基脲、喹唑啉和2,5 - 二取代1,3,4 - 噻二唑作为抗惊厥药效基团的重要性,促使我们开展了三个新型含1,3,4 - 噻二唑和喹唑啉环的氨基脲系列化合物的合成。通过元素分析和光谱(红外光谱、1H核磁共振、13C核磁共振和质谱)分析阐明了这些化合物的化学结构。使用最大电休克惊厥(MES)和皮下注射戊四氮(scPTZ)模型研究了这些化合物的抗惊厥活性。进行转棒试验以评估神经毒性。在生物筛选中发现大多数化合物具有活性。本研究结果证明,四结合位点药效基团模型对抗癫痫活性起决定性作用。还尝试建立了合成化合物之间的构效关系。