Citation: 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]. Chinese Journal of Organic Chemistry, ;2017, 37(2): 385-393. doi: 10.6023/cjoc201608031 shu

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

Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002

Corresponding author: Chen Hua, hua-todd@163.com Li Xiaoliu, lixl@hbu.cn
Received Date: 31 August 2016
Revised Date: 8 October 2016

Fund Project: National Natural Science Foundation of China 21372060the Natural Science Fund for Distinguished Young Scholars of Hebei Province (Incubation) B2015201005

Figures(2)

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%.
- quinazolin-4-one,
- N-/O-alkylation,
- anti-tumor activity,
- antimicrobial activity
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