El Ashry El Sayed H, Ramadan El Sayed, Amer Mohammed R, El Kilany Yeldez, Badawy Mohamed E I, Rabea Entsar I
Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21524, Egypt.
International Center for Chemical and Biological Science, H.E.J. Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan.
Curr Org Synth. 2019;16(5):801-809. doi: 10.2174/1570179416666190415113847.
5-Amino-2-alkyl/glycosylthio-1,3,4-thiadiazoles have been synthesized by the reaction of 5-amino-1,3,4-thiadiazole-2-thiol with a variety of alkylating agents or glycosyl halides in the presence of anhydrous potassium carbonate in dry acetone.
The structures of the newly synthesized compounds have been established based on their spectral data (FT-IR, 1H- and 13C-NMR) and mass spectrometry. They were tested for their antioxidant behaviour by the use of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. The in silico pharmacokinetics ADME properties of the potent antioxidant compounds were investigated by using Accelrys Discovery Studio (DS) 2.5 software.
Regioselective alkylation and glycosylation of 5-amino-1,3,4-thiadiazole-2-thiol were noticed during its reaction with alkylating agents and glycosyl halides. Alkylating agents gave the Sfunctionalized derivatives, while the acetylated glycosyl halides afforded the S-glycosylated products together with their respective N-acetyl derivatives. The benzoylated glycosyl halide behaved in a different manner and gave N-glycoside analogue of 1,3,4-thiadiazole-2(3H)-thione, in addition to the expected sulfanyl S-glycoside. Most of the synthesized compounds showed noticeable antioxidant activity with respect to ceftriaxone as a standard drug. Some of the most active compounds showed acceptable predicted pharmacokinetics and druglikeness properties.
通过使5-氨基-1,3,4-噻二唑-2-硫醇与多种烷基化剂或糖基卤化物在无水碳酸钾存在下于干燥丙酮中反应，合成了5-氨基-2-烷基/糖基硫代-1,3,4-噻二唑。
基于新合成化合物的光谱数据（傅里叶变换红外光谱、氢核磁共振谱和碳核磁共振谱）以及质谱确定了它们的结构。通过使用2,2-二苯基-1-苦基肼基（DPPH）自由基清除法测试了它们的抗氧化行为。使用Accelrys Discovery Studio（DS）2.5软件研究了强效抗氧化化合物的计算机模拟药代动力学ADME性质。
在5-氨基-1,3,4-噻二唑-2-硫醇与烷基化剂和糖基卤化物反应过程中，观察到了区域选择性烷基化和糖基化。烷基化剂生成了S-官能化衍生物，而乙酰化糖基卤化物除了生成相应的N-乙酰基衍生物外，还得到了S-糖基化产物。苯甲酰化糖基卤化物表现不同，除了预期的硫烷基S-糖苷外，还生成了1,3,4-噻二唑-2(3H)-硫酮的N-糖苷类似物。相对于作为标准药物的头孢曲松，大多数合成化合物显示出显著的抗氧化活性。一些最具活性的化合物显示出可接受的预测药代动力学和类药性质。
