新型6-氟-4(3H)-喹唑啉酮类Schiff碱的合成及其抑菌活性
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摘要
以2-氨基-5-氟苯甲酸为起始原料,与醋酐酰化关环制得6-氟-2-甲基噁嗪-4-酮(1); 1在80%水合肼中回流反应制得6-氟-2-甲基-3-氨基-4(3H)-喹唑啉酮(2); 2分别与羟基芳醛和杂环芳醛反应合成了6个6-氟-4(3H)-喹唑啉酮类Schiff碱(3a～3f),其中3b～3f为新化合物,其结构经~1H NMR,~(13)C NMR,IR和元素分析表征。采用琼脂扩散法研究了3a～3f对大肠杆菌、金黄色葡萄球菌和枯草杆菌的抑制活性。结果表明:用药浓度为400μg·mL~(-1)时,3a～3f对受试菌种均有一定的抑制活性,其中6-氟-2-甲基-3-(4-吡咯苯亚甲氨基)-4(3H)-喹唑啉酮(3c)抑菌活性最强,对大肠杆菌和枯草杆菌的抑菌圈直径分别为9. 38 mm和9. 00 mm。
3-Amino-6-fluoride-2-methyl-4( 3H)-quinazolinone( 2) was prepared by 80% N_2H_4·H_2O and 6-fluoride-2-methyl-3,1-benzoxazin-4-one,which was obtained using 5-fluoride-anthranilic acid as the raw material by cyclization with acetic anhydride. Six 6-fluoride-4( 3H)-quinazolinone Schiff bases( 3a ～ 3f) were synthesized by the reaction of 2 with hydroxyl/heterocyclicaromaticaldehyde. Among them,3b ～ 3f were new compounds. The structures were characterized by1 H NMR,13 C NMR IR,and elementary analysis. The preliminary antibacterial activities of 3a ～ 3f against Escherichia coli,Staphylococcus aureus and Bacillus subtilis were investigated by agar diffusion method. The results showed that3 a ～ 3f exhibited certain antibacterial activities with concentration of 400 μg·m L~(-1) and 6-fluoride-2-methyl-(( 4-pyrryl) methylene amimo)-4( 3H)-quinazolinone( 3c) produced 9. 38 mm and 9. 00 mminbibition zone diameters against Escherichia coli and Bacillus subtilis,respectively.
3-Amino-6-fluoride-2-methyl-4( 3H)-quinazolinone( 2) was prepared by 80% N_2H_4·H_2O and 6-fluoride-2-methyl-3,1-benzoxazin-4-one,which was obtained using 5-fluoride-anthranilic acid as the raw material by cyclization with acetic anhydride. Six 6-fluoride-4( 3H)-quinazolinone Schiff bases( 3a ～ 3f) were synthesized by the reaction of 2 with hydroxyl/heterocyclicaromaticaldehyde. Among them,3b ～ 3f were new compounds. The structures were characterized by1 H NMR,13 C NMR IR,and elementary analysis. The preliminary antibacterial activities of 3a ～ 3f against Escherichia coli,Staphylococcus aureus and Bacillus subtilis were investigated by agar diffusion method. The results showed that3 a ～ 3f exhibited certain antibacterial activities with concentration of 400 μg·m L~(-1) and 6-fluoride-2-methyl-(( 4-pyrryl) methylene amimo)-4( 3H)-quinazolinone( 3c) produced 9. 38 mm and 9. 00 mminbibition zone diameters against Escherichia coli and Bacillus subtilis,respectively.
引文
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[24]刘杰,王慧峰,陆娟,等.新型6-氯-4(3H)-喹唑啉酮类Schiff碱的合成及其抑菌活性[J].合成化学,2016,24(11):942-945.
[2] GOMHA S M,AHMED S A,ABDELHAMID A O.Synthesis and cytotoxicity evaluation of some novel thiazoles,thiadiazoles and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones in corporating triazole moiety[J]. Molecules,2015,20(1):1357-1376.
[3] WANG X,YIN J,SHI L,ZHANG G,et al. Design,synthesis and antibacterial activity of novel Schiff base derivatives of quinazolin-4(3H)-one[J]. Eur J Med Chem,2014,77:65-74.
[4] KULABAS N,TATAR E,BINGOL OZAKPINR O,et al. Synthesis and antiproliferative evaluation of novel2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells[J]. Eur J Med Chem,2016,121:58-70.
[5]李鹏程,刘刚,曹琨,等.喹唑啉类化合物抗癌活性研究进展[J].中国药学杂志,2016,51(11):867-874.
[6] HE L,FAN F,HOU X,et al. 4(3H)-Quinazolone regulates innate immune signaling upon respiratory syncytial virus infection by moderately inhibiting the RIG-1 pathway in RAW264. 7 cell[J]. Int Immunopharmacol,2017,52:245-252.
[7]王翔,汤承浩,蒋向辉,等.喹唑啉衍生物的合成及农药生物活性研究进展[J].农药学报,2017,19(2):131-151.
[8]李婵,宋少洁,胡煜堃,等.抗真菌药阿巴康唑的合成工艺改进[J].中国药物化学杂志,2017,27(1):35-19.
[9]魏海东. 4(3H)-喹唑啉酮的绿色合成与结构分析[D].成都:成都理工大学,2015.
[10]杨绪红,王翔,吴鸣虎. 2-芳氨基-3-羟乙基喹唑啉-4-(3H)-酮衍生物的合成及生物活性[J].有机化学,2014,34(4):1015-1020.
[11]王大伟,林红艳,曹润洁,等.含喹唑啉二酮片段的新型三酮类化合物的合成及生物活性[J].化学学报,2015,73(1):29-35.
[12] ZHANG J,CHENG P,MA Y,LIU J,et al. An efficient nano Cu O-catalyzed synthesis and biological evaluation of quinazolinone Schiff base derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones as potent antibacterial agents against Streptococcuslactis[J]. Tetrahedron Lett,2016,57(47):5271-5277.
[13] KHAN I,IBRAR A,ABBAS N,et al. Recent advances in the structural library of functionalized quinazoline and quinazolinone scaffolds:Synthetic approaches and multifarious applications[J]. Eur J Med Chem,2014,76:193-244.
[14] EL-HASHASH M A,ELSHAHAWI M M,RAGAB E A,et al. Synthesis and antifungal activity of novel quinazolin-4(3H)-one derivatives[J]. Synthetic Commun,2015,45(19):2240-2250.
[15]潘顶伍,杜欢,吕新阳,等.含1,2,4-三唑席夫碱的新型喹唑啉-2,4-二酮类衍生物的合成及其抗细菌活性研究[J].有机化学,2016,36(4):818-825.
[16]杜欢,范治江,杨岚,等.含喹唑啉-4-酮片段的新型1,2,4-三唑酰腙类衍生物的合成及抗菌作用[J].有机化学,2018,38(2):531-538.
[17]孙佳倩,周立凯,谭官海,等.喹唑啉-4-酮衍生物的合成及抗肿瘤活性[J].有机化学,2017,37(2):455-461.
[18] PATER R V,KUMARI P,RAJANI D P,et al. Discovery of 2-(4-cyano-3-triflunoomethylphenyl amino)-4-(4-quinazolinyloxy)-6-piperiazinyl(piperidinyl)-s-triazines as potential antibacterial agents[J].Med Chem Res,2012,21(12):4177-4192.
[19]王水英,刁海鹏,傅力明. 2-羟基-1萘醛缩对氨基水杨酸希夫碱铬配合物的合成及体外抗肿瘤活性研究[J].中国药物与临床,2016,16(8):1096-1098.
[20]周学拳.席夫碱与酰腙类金属配合物的合成及抗癌活性研究[D].天津:南开大学,2016.
[21]吕秀文.昆布氨酸及其席夫碱过渡金属配合物的合成、表征及生物活性研究[D].青岛:中国海洋大学,2014.
[22] KORATAEV V Y,BARKOV A Y,KOTOVICH I V,et al. Three-component synthesis of substitutedβ-(trifluoromethyl)pyrroles via Grob cyclization of 1,1,1-trifluoro-3-nitrobut-2-ene with 1,3-dicarbonylic compounds and ammonia or primary amines[J]. J Fluorine Chem,2012,138(40):42-47.
[23] HOSAMANI K M,REDDY D S,DEFARAJEGOWDA H C. Microwave-assisted synthesis of new fluorinated coumarin-pyrimidine hybrids as potent anticancer agents,their DNA cleavage and X-ray crystal studies[J]. RSC Adv,2015,5(15):11261-11271.
[24]刘杰,王慧峰,陆娟,等.新型6-氯-4(3H)-喹唑啉酮类Schiff碱的合成及其抑菌活性[J].合成化学,2016,24(11):942-945.