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

doi:10.6023/cjoc201608031

Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (2): 385-393.DOI: 10.6023/cjoc201608031 Previous Articles Next Articles

ARTICLE

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

王淑霞, 高梦颖, 谭官海, 马海霞, 赵莹莹, 杜鸿源, 王总帅, 陈华, 李小六

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

收稿日期:2016-08-31 修回日期:2016-10-08 发布日期:2016-11-03
通讯作者: 陈华, 李小六 E-mail:lixl@hbu.cn;hua-todd@163.com
基金资助:
国家自然科学基金（No.21372060）及河北省自然科学杰出青年基金（培育）（No.B2015201005）资助项目.

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

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

Received:2016-08-31 Revised:2016-10-08 Published:2016-11-03
Supported by:
Project supported by the National Natural Science Foundation of China (No. 21372060) and the Natural Science Fund for Distinguished Young Scholars of Hebei Province (Incubation) (No. B2015201005).

1. 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.PDF(2482KB)

Abstract

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 S_N2 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%.

Key words: quinazolin-4-one, N-/O-alkylation, anti-tumor activity, antimicrobial activity

Cite this article

Wang Shuxia, Gao Mengying, Tan Guanhai, Ma Haixia, Zhao Yingying, Du Hongyuan, Wang Zongshuai, Chen Hua, Li Xiaoliu. 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[J]. Chin. J. Org. Chem., 2017, 37(2): 385-393.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Khan, I.; Zaib, S.; Batool, S.; Abbas, N.; Ashraf, Z.; Iqbal, Jamshed.; Saeed, A. Bioorg. Med. Chem. 2016, 24, 2361.
[2] Khan, I.; Ibrar, A.; Abbas, N.; Saeed, A. Eur. J. Med. Chem. 2014, 76, 193.
[3] Yan, B. R.; Lv, X. Y.; Du, H.; Bao, X. P. Chin. J. Org. Chem. 2016, 36, 207 (in Chinese).(闫柏任, 吕新阳, 杜欢, 鲍小平, 有机化学, 2016, 36, 207.)
[4] Ou, J. J.; Liu, K. C.; Wang, Y.; Zhang, H.; Liu, R. Q.; Li, Q. B.; Wang, Q. M.; Li, Y. Q.; Rui, C. H.; Liu, S. Z. Chin. J. Org. Chem. 2014, 34, 526 (in Chinese).(欧俊军, 刘克昌, 王毅, 张浩, 刘瑞全, 李奇博, 汪清民, 李永强, 芮昌辉, 刘尚钟, 有机化学, 2014, 34, 526.)
[5] Xu, W.; Jin, Y. B.; Liu, H. X.; Jiang, Y. Y.; Fu, H. Org. Lett. 2011, 13, 1274.
[6] Liu, C. E.; Yu, Q. Y.; Tang, J. H.; Li, J. R. Chin. J. Org. Chem. 2012, 32, 532 (in Chinese).(刘长娥, 于琪瑶, 唐健红, 李加荣, 有机化学, 2012, 32, 532.)
[7] Khan, I.; Ibrar, A.; Ahmed, W.; Saeed, A. Eur. J. Med. Chem. 2015, 90, 124.
[8] Usifoh, C. O.; Scriba, G. K. E. Pharm. Med. Chem. 2000, 333, 261.
[9] Hori, M.; Ohtaka, H. Chem. Pharm. Bull. 1993, 41, 1114.
[10] Chen, G. S.; Kalchar, S.; Kuo, C.-W.; Chang, C.-S.; Usifoh, C. O.; Chern, J.-W. J. Org. Chem. 2003, 68, 2502.
[11] Bogentoft, C.; Krongberg, L.; Danielsson, B. Acta Pharm. Suec. 1969, 6, 489.
[12] Chen, H.; Li, S.; Yao, Y. C.; Zhou, L. K.; Zhao, J. P.; Gu, Y. J.; Wang, K. R.; Li, X. L. Bioorg. Med. Chem. Lett. 2013, 23, 4785.
[13] Wang, Z. Z.; Tang, Y. Tetrahedron 2016, 72, 1330.
[14] Kim, N. Y.; Cheon, C.-H. Tetrahedron Lett. 2014, 55, 2340.
[15] Roopan, S. M.; Maiyalagan, T.; Khan, F. N. Can. J. Chem. 2008, 86, 1019.
[16] Shang, Y. H.; Fan, L. Y.; Li, X. X.; Liu, M. X. Chin. Chem. Lett. 2015, 26, 1355.
[17] Adib, M.; Ansari, S.; Mohammadi, A.; Bijanzadeh, H. R. Tetrahedron Lett. 2010, 51, 30.
[18] Zhan, D.; Li, T. B.; Zhang, X. P.; Dai, C.; Wei, H. H.; Zhang, Y. Y.; Zeng, Q. L. Synth. Commun. 2013, 43, 2493.
[19] Mosmann, T. J. Immunol. Methods 1983, 65, 55.

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

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Yan Zeng, Lifei Nie, Chao Niu, Aytilla Mamatjan, Khurshed Bozorov, Jiangyu Zhao, Haji Akber Aisa. Synthesis and Biological Activities of Dihydrooxazolo[5,4-d]-pyrrolo[1,2-a]pyrimidinones [J]. Chinese Journal of Organic Chemistry, 2022, 42(2): 543-556.
[2]	Yujia Sun, Ziwei Wang, Yan Wang, Tongxiu Xu, Keqing Tian, Ping Zhang. Synthesis and Antimicrobial Activity of 1,5-Benzothiazepines Incorporated with Triazole Moiety [J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2361-2373.
[3]	Jun Shi, Na Luo, Muhan Ding, Chuanhui Li, Suran Wan, Peijia Li, Junhong Li, Xiaoping Bao. Synthesis and Antimicrobial Activities of Novel 1,3,4-Oxa(Thia)- diazole Derivatives Containing 6-Fluoroquinazoline Moiety [J]. Chinese Journal of Organic Chemistry, 2021, 41(2): 738-756.
[4]	Zhang Yan, Wang Yunyun, Zhao Yuxun, Zhang Chenglong, Gu Wen, Wang Zhonglong, Zhu Yongqiang, Wang Shifa. Camphor-Based Thiosemicarbazone Analogues Induced G2 Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species (ROS)-Mediated Mitochondrial Pathway in Human Breast Cancer Cells [J]. Chinese Journal of Organic Chemistry, 2020, 40(8): 2374-2386.
[5]	Yuan Rui, Cui Hao, Chen Wen, Ren Xuanxuan, Zhou Hang, Xu Hui, Sun Yawen, Liang Yanni, Wan Yu, Liu Jinjuan, Wu Hui. Synthesis of 1,7-Bis(N-substituted-aminomethyl)-2,8-dihydroxy-Tröger's Bases and Their Application in Aldol-Ullmann Reaction [J]. Chinese Journal of Organic Chemistry, 2020, 40(4): 1017-1027.
[6]	Zhang Xiangna, He Feng, Zhang Qiuqiong, Lü Jiahui, Xu A'na, Yu Chenggong, Qu Ying, Wu Jingde. Design, Synthesis and Evaluation of Anti-tumor Activities of Chidamide Derivatives [J]. Chin. J. Org. Chem., 2019, 39(7): 1983-1989.
[7]	Yu Haihong, Zhou Shengchao, Guo Tingting, Liang Zhuo, Chen Huabin, Dai Weikai, Song Mingxia. Synthesis and Antimicrobial Activity Evaluation of Aminoguanidine Derivatives Containing a Biphenyl Moiety [J]. Chin. J. Org. Chem., 2019, 39(5): 1497-1502.
[8]	Niu Liping, Xing Shunkai, Li Xiaoliu, Chen Hua. Synthesis of the Fused Tetracyclic Thiazinan-4-one Derivatives and Their Anti-tumor Activitiy [J]. Chin. J. Org. Chem., 2019, 39(3): 771-777.
[9]	Liao Shili, Zhang Guogai, Cao Han, Chen Biying, Li Weimin, Wu Xia, Feng Yifan. Synthesis and Anti-tumor Activities against HepG2 Cell in vitro of the Conjugates of Honokiol, Quercetin and Berberine [J]. Chin. J. Org. Chem., 2018, 38(6): 1549-1555.
[10]	Li Lingdong, Chi Xiaofang, Yan Jiawei, Zhao Zihan. Synthesis and Immobilization of Pyridinium N-Chloramine Precursors on PU Film for Antibacterial Application [J]. Chin. J. Org. Chem., 2018, 38(4): 955-962.
[11]	Du Huan, Fan Zhijiang, Yang Lan, Bao Xiaoping. Synthesis and Antimicrobial Activities of Novel 1,2,4-Triazole-acyl-hydrazone Derivatives Containing the Quinazolin-4-one Moiety [J]. Chin. J. Org. Chem., 2018, 38(2): 531-538.
[12]	Ma Fuli, Zhang Jiao, Li Ming, Yu Jiaying, Luo Wei, Li Xueqiang, Wei Mengxue. Synthesis of Novel Matrine Derivatives Containing Furanone Skeleton and Preliminary Evaluation of Their Anticancer Activity in Vitro [J]. Chin. J. Org. Chem., 2018, 38(10): 2633-2638.
[13]	Meng Yanqiu, Xing Wen, Kuai Zhenyu, Zhang Weichen, Li Wei. Synthesis and Anti-Tumor Activities of Ring A Derived Analogues of Oleanolic Acid [J]. Chin. J. Org. Chem., 2017, 37(6): 1417-1425.
[14]	Zhao Kai, Wang Shuai, Zhan Xiaoping, Liu Zenglu, Mao Zhenmin. Synthesis and Anti-tumor Activity of 4-(Methoxyl thienyl)-3- (substituted benzoyl)pyrroles [J]. Chin. J. Org. Chem., 2017, 37(4): 943-953.
[15]	Sun Jiajing, Zhou Likai, Tan Guanhai, Li Shuai, Wang Shuxia, Chen Hua, Li Xiaoliu. Synthesis and Anti-tumor Activity of Novel Quinazolin-4-one Derivatives [J]. Chin. J. Org. Chem., 2017, 37(2): 455-461.