新型2-(取代苄硫基)-5-(4,6-二甲基嘧啶-2-硫甲基)-1,3,4-噁二唑化合物的合成及生物活性
收稿日期: 2018-04-25
修回日期: 2018-06-24
网络出版日期: 2018-07-05
基金资助
国家自然科学基金（No.30900959）和浙江省自然科学基金（No.LY17C140003）资助项目.
Synthesis and Biological Activity of Novel 2-(Substituted-benzylthio)-5-(4,6-dimethylpyrimidin-2-thiomethyl)-1,3,4-oxadiazoles
Received date: 2018-04-25
Revised date: 2018-06-24
Online published: 2018-07-05
Supported by
Project supported by the National Natural Science Foundation of China (No. 30900959) and the Zhejiang Provincial Natural Science Foundation (No. LY17C140003).
为寻找新型杂环活性化合物，通过活性亚结构拼接方法，以硫脲和乙酰丙酮为起始原料合成4，6-二甲基嘧啶-2-硫醇，随后经醚化、肼化、环化反应，最后与取代苄氯在微波辐射中合成得到13个新型2-（取代苄硫基）-5-（4，6-二甲基嘧啶-2-硫甲基）-1，3，4-噁二唑化合物.生物活性测试结果表明，在50 μg/mL浓度下，部分化合物对尖孢炭疽病菌、枸杞炭疽病菌、草莓炭疽病菌具有较好的杀菌活性，其中取代基为3-氟时对尖孢炭疽病菌的抑制率达到80.22%；若干化合物还表现出良好的抗杜氏利什曼原虫活性，其中取代基为3-氯，4-溴，3-氟和4-叔丁基时，IC50值均低于25 μg/mL，优于对照药剂巴龙霉素.
汪洲洋 , 徐涵靖 , 赵建平 , 刘幸海 , 翁建全 . 新型2-(取代苄硫基)-5-(4,6-二甲基嘧啶-2-硫甲基)-1,3,4-噁二唑化合物的合成及生物活性[J]. 有机化学, 2018 , 38(11) : 3112 -3117 . DOI: 10.6023/cjoc201804044
In order to find novel biologically active heterocyclic compounds, thirteen new 2-(substitutedbenzylthio)-5-(4,6-dimethylpyrimidin-2-thiomethyl)-1,3,4-oxadiazoles were prepared with thiocarbamide and 2,4-pentanedione as the staring materials via cyclization, etherification, hydrazination, cyclization and finally a benzylation reaction under microwave irradiation condition. The preliminary bioassay results indicated that some target compounds exhibited good inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 μg/mL, and the inhibition rate of the compound with 3-fluoro against Colletrotichum acutatum reached 80.22%. Several compounds also showed that good antileishmanial activities against Leishmania donovani, the IC50 values of those compounds with 3-chloro, 4-bromo, 3-fluoro and 4-tert-butyl substituent respectively were all less than 25 μg/mL and were more active than the control drug paromomycin.
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