C-2苯环上取代基对喹唑啉-4-酮烷基化的影响及化合物抗肿瘤、抗菌活性  

Effects of the Substituent at C-2 Phenyl on the N-/O-Alkylation of Quinazolin-4(3H)-one and Anti-Tumor, Antimicrobial Activities of Some Compounds

作　　者：王淑霞[1] 高梦颖[1] 谭官海 马海霞[1] 赵莹莹[1] 杜鸿源 王总帅 陈华[1] 李小六[1] Wang Shuxia Gao Mengying Tan Guanhai Ma Haixia Zhao Yingying Du Hongyuan Wang Zongshuai Chen Hua Li Xiaoliu(Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002)

机构地区：[1]河北大学化学与环境科学学院河北省化学生物学重点实验室,保定071002

出　　处：《有机化学》2017年第2期385-393,共9页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.21372060);河北省自然科学杰出青年基金(培育)(No.B2015201005)资助项目~~

摘　　要：邻氨基苯甲酰胺与取代苯甲醛反应,合成了含氨烷基侧链的喹唑啉-4-酮4和5,探讨了C-2位苯环取代基对喹唑啉-4-酮内酰胺N-/O-烷基化的影响,并评价了部分化合物的抗肿瘤细胞增殖活性及抑菌活性.结果表明,当C-2苯环上的取代基在邻位时,N-烷基化反应为主;而在间位或对位时,以O-烷基化为主,立体效应起到了主导作用.4-{2-{{2-[3-(苄氧基)苯基]喹唑啉-4-基}氧基}乙基}吗啉(4h)具有较好的抗肺癌细胞增殖活性,IC_(50)值为13.20μmol/L.2-(2-氯苯基)-3-[2-(哌啶-1-基)乙基]喹唑啉-4(3H)-酮(5aa)和2-[3-(苄氧基)苯基]-4-[2-(吡咯啉-1-基)乙氧基]喹唑啉(4hb)(50μg/m L)对大肠杆菌和痢疾杆菌具有显著的抑制活性,抑菌率分别为100%,100%和100%,96%.化合物5aa对链铬孢菌真菌的抑制率为100%.A series of quinazolin-4（3H）-one derivatives 4 and 5 possessing amino alkyl side chain were synthesized by the condensation reaction of 2-aminobenzamide with substituted benzaldehyde, followed by SN2 substitution reaction with haloalkane. The effects of the substituent at C-2 phenyl on the N-/O-alkylated reaction of quinazolin-4（3H）-one were explored. Some compounds were also evaluated for their anti proliferation activities and antimicrobial activities. The results showed that when the substituent was at orth O-position on C-2 phenyl, N-alkylation was the main reaction, while at meta- or para-positions, O-alkylation was predominant, which suggested that the steric factor played a key role on this ambident nuclophilic substitution. 4-（2-（（2-（3-（Benzyloxy）phenyl）quinazolin-4-yl）oxy）ethyl）morpholine （4h） showed relatively good anti-proliferative activity against A549 tumor cells with the IC50 value of 13.20 μmol/L. 2-（2-Chlorophenyl）-3-（2-（piperidin-1-yl）ethyl）quinazolin-4（3H）-one （5aa） and 2-（3-（benzyloxy）phenyl）-4-（2-（pyrrolidin-1-yl）ethoxy）quinazoline （4hb） exhibited significant anti Esche-richia coli or Shigella castellani activities, and the inhibition rates were near 100% at the concentration of 50 μg/mL. The inhi-bition rate of compound 5aa against Alternaria alternate was 100%.

关 键 词：喹唑啉-4-酮 N-/O-烷基化 抗肿瘤活性 抗菌活性 

分 类 号：TQ460.1[化学工程—制药化工]