Synthesis of substituted novel quinazolinone compounds
-
摘要: 目的 优化取代喹唑啉酮类化合物的合成工艺,重点考察温度、时间2个因素对关键中间体化合物合成的影响。 方法 平行试验比较温度、时间和缩合剂催化酯键的氨解反应,并对试验结果进行整体化分析;采用正交设计的方差分析考察反应物、温度及时间对收率的影响。 结果 和 结论 所得化合物的结构经过1H NMR、MS和13C NMR等方法确证,当反应温度为30 ℃,反应时间为24 h,缩合剂(DCC)与反应物的投料比为1.5:1时,酯键氨解反应的收率最高(65.41%),使得取代喹唑啉酮类化合物的合成路线更加符合工业生产的要求。体外抗真菌活性实验结果表明,所测定的先导化合物对5种临床致病菌都具有潜在的抗真菌活性,值得进一步研究。Abstract: Objective To optimize the synthesis route of substituted quinazolinone and investigate the influence of temperature and time in the synthesis of key intermediates. Methods A parallel test was carried out to compare temperature, time and the ester bond ammonolysis of condensing agent, including the total analysis of experimental result. And orthogonal experimental design was used and the influence of temperature and time on the yield were investigated. Results and Conclusion The structure of the compound was confirmed by 1H NMR, MS and 13C NMR. When the reaction temperature was 30 ℃, the reaction time was 24 h with the condensing agent (DCC) and the reactant ratio of 1.5:1, the yield of ester bond ammonolysis was higher. The optimal preparation procedure of quinazolinone compounds was more available for industrial production. In vitro antifungal activity test Results showed that the lead compounds measured on five clinical pathogenic fungi have the potential antifungal activity, and are worth for further study.
-
Key words:
- quinazolinone compound /
- synthesis /
- orthogonal design /
- analysis of variance
-
[1] 刘 刚,李晓燕.喹唑啉酮类化合物合成新方法研究进展[J].药学进展, 2007,31(12): 542-550. [2] 佟茂国.喹唑啉类化合物的合成及其抗肿瘤活性研究进展[J].广州化工,2012,40(3),17-19. [3] Chandrika P M,Yakaiah T,Gayatri G,et al.Click chemistry: studies on the synthesis of novel fluorous tagged triazol -4 -yl substituted quinazoline derivatives and their biological evaluation-theoretical and experimental validation[J].Eur J Med Chem,2010,45: 78-84. [4] El-Gazzar ABA,Youssef MM,Youssef AM S,et al.Design and synthesis of azolopyrimidoquinolines,pyrimidoquinazolines as anti-oxidant,anti-inflammatory and analgesic activities[J].Eur J Med Chem,2009,44: 609-624. [5] 李文举,欧阳贵平,张广龙.4-取代氨基喹唑啉类化合物的研究进展[J].精细化工中间体,2009,39(3),15-20. [6] Lee JY,Park YK,Seo SH,et al.1,4-dioxane-fused 4-anilinoquinazoline as inhibitors of epidermal growth factor receptor kinase[J]. Arch Pharm Res,2001, 334(11):357-360. [7] Lee JY,Lee YS,Park HK, et al.4-(Phenylamino)[1,4] dioxano[2,3-g] quinazoline derivatives and process for preparing the same: USA,2003045537[P]. 2003-03-06. [8] 宁微微,刘雪飞,张晓梦,等.新型喹唑啉酮类先导物的设计、合成及抑制人顶体酶活性研究[J].药学实践杂志,2010,28(4),296-298,312. [9] Ioannis K,Abdelhakim E,Elisabeth S,et al.Rapid synthesis of 2,3-disubstituted-quinazolin-4-ones enhanced by microwave-assisted decomposition of formamide [J]. Tetrahedron Lett,2007, 48: 6609. [10] 宋桂红,张 珏,张晓梦,等.南德士抑制人精子顶体酶活性的实验研究[J].中华男科学杂志, 2009, 15(8): 700. [11] 付丙月,唐 辉,郑灿辉,等.四氢萘类化合物合成工艺研究[J].药学实践杂志,2012,30(1),35-37. [12] NCCLS.Reference method for broth dilution antifungal susceptibility testing of yeasts;approved standard[S].2nd ed.Villanova:[s.n.],2000. [13] 曹永兵,姜远英,王 宁,等.微量液基稀释法测定化合物特苄康唑的体外抗真菌活性[J].中国抗生素杂志, 2000, 25, 183. 期刊类型引用(1)
1. 孙远东，周千喜，吕明月，张璇，苏国振，聂学刚. 新型喹唑啉酮衍生物的合成、结构及荧光性质研究. 萍乡学院学报. 2021(03): 59-63 . 
百度学术其他类型引用(0)
-
点击查看大图
计量
- 文章访问数: 3903
- HTML全文浏览量: 354
- PDF下载量: 240
- 被引次数: 1
下载:
