Synthesis and in vitro antibacterial evaluation of novel imidazo[2′,1′:5,1]-1,2,4-triazolo[4,3-c]-quinazoline derivatives of 5-thioxo-1,2,4-triazole, 4-oxothiazolidine, and their open-chain counterparts
Synthesis and in vitro antibacterial evaluation of novel imidazo[2′,1′:5,1]-1,2,4-triazolo[4,3-c]-quinazoline derivatives of 5-thioxo-1,2,4-triazole, 4-oxothiazolidine, and their open-chain counterparts
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DOI：
10.1002/ardp.200300809
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发表时间：
2003-12-01
影响因子：
5.1
通讯作者：
El-Bendary, ER
中科院分区：
文献类型：
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作者：
Nasr, MN;Gineinah, MM;El-Bendary, ER
以相应的氨基硫脲衍生物5a-f为原料，合成了两个新的咪唑并[2 '，1'：5，1]-1，2，4-三唑并[4，3-c]喹唑啉衍生物6a-f和4-氧代噻唑烷衍生物7a-f。用于制备化合物5a-f的逐步方法是以母体3-氨基-1，2，4-三唑并[4，3-c]喹唑啉2与2-氯乙酰乙酸乙酯反应开始，导致咪唑环的加成，得到酯3a-c。然而，这些酯衍生物的肼解得到相应的酰肼4a-c，其与适当的异硫氰酸烷基酯反应得到化合物5a-f。依次用氢氧化钾或溴乙酸乙酯环化化合物5，分别得到相应的硫代三唑6和氧代噻唑烷7。所有合成的化合物进行了筛选，其在体外抗菌活性对各种革兰氏阳性和革兰氏阴性细菌。发现一些测试化合物具有有效的抗菌活性。化合物7 f对两种类型的细菌，特别是革兰氏阳性生物体表现出比参考标准环丙沙星高得多的效力。
Two novel series of imidazo[2',1':5,1]-1,2,4-triazolo[4,3-c]quinazolines bearing 5-thioxo-1,2,4-triazoles, 6a-f and 4-oxothiazolidines, 7a-f, were synthesized from corresponding thiosemicarbazide derivatives, 5a-f. The stepwise methodology applied to the preparation of compounds 5 a-f was initiated with reaction of the parent 3-amino-1,2,4-triazolo[4,3-c]quinazolines, 2, with ethyl 2-chloroacetoacetate resulting in annelation of the imidazole ring to give esters, 3 a-c. However, hydrazinolysis of these ester derivatives gave the corresponding acid hydrazides, 4a-c, which on reaction with the appropriate alkyl isothiocyanate yielded compounds 5a-f. In turn, compounds 5, were cyclized with potassium hydroxide or with ethyl bromoacetate to give the corresponding thioxotriazoles 6 and oxothiazolidines 7, respectively. All synthesized compounds were screened for their in vitro antibacterial activity against various Gram-positive and Gram-negative bacteria. Some test compounds were found to possess potent antibacterial activities. Compound, 7f, exhibited much higher potency than the reference standard ciprofloxacin, against both types of bacteria, particularly, Gram-positive organisms.