Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi, India.
Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi, India.
Bioorg Chem. 2020 Jun;99:103584. doi: 10.1016/j.bioorg.2020.103584. Epub 2020 Jan 27.
Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.
哒嗪酮类似物已被证明是有希望的抗惊厥药物候选物。我们已经确定了几种哒嗪酮类抗惊厥药物。作为我们之前研究的延续，设计并合成了一系列通过酰胺键连接的哒嗪酮-噻唑杂合体。其中，化合物 SP-5F 表现出显著的抗惊厥活性，MES 中位数有效剂量为 24.38 mg/kg，scPTz 中位数有效剂量为 88.23 mg/kg。GABA 测定结果显示，与对照组相比，GABA 水平显著增加。在 GABA 受体活性位点的分子对接研究进一步证实了 SP-5F 的 GABA 调节作用。
