Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (5): 1233-1241.DOI: 10.6023/cjoc201708027 Previous Articles     Next Articles



黄新炜a, 刘建利b   

  1. a 西安文理学院化学工程学院 西安 710065;
    b 西北大学生命科学学院 西部资源生物与现代生物技术省部共建教育部重点实验室 西安 710069
  • 收稿日期:2017-08-14 修回日期:2017-10-31 发布日期:2018-01-03
  • 通讯作者: 黄新炜,
  • 基金资助:


Synthesis and Anticancer Activities of Novel Pyranocoumarin Fused Pyrimidine Based on Cyanoenamine

Huang Xinweia, Liu Jianlib   

  1. a School of Chemical Engineering, Xi'an University, Xi'an 710065;
    a Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Science, Northwest University, Xi'an 710069
  • Received:2017-08-14 Revised:2017-10-31 Published:2018-01-03
  • Contact: 10.6023/cjoc201708027
  • Supported by:

    Project supported by the Science and Technology Program of Xi'an City (No. CXY1443WL13) and the Foundation of the Education Department of Shaanxi Province (No. 15JK2145).

Pyranocoumarin is an important kind of natural products, which has many biological activities and pharmacological effects, such as antitumor, anti-bacterial, anti-human immunodeficiency virus (HIV), anti-inflammatory, antioxidation, etc. Pyrimidine is another important nitrogen-containing heterocycles. Using the pharmacophore combination principle of drug design, it is possible to obtain lead compounds with better anticancer activities by puting pyranocoumarin and pyrimidine structures together. Therefore, pyranocoumarin which has cyanoenamine structure was synthesized by multicomponent reaction, taking 4-hydroxycoumarin, aromatic aldehyde, malononitrile as raw materials and 4-dimethylaminopyridine (DMAP) as catalyst. Then N, N-dimethyl formamidine derivatives were synthesized by treatment with dimethylformamide-dimethyl acetal. Finally 4-anilino substituted pyranocoumarin fused pyrimidines were synthesized by treatment with substituted anilines involving Dimroth rearrangement. The structures of target compounds were characterized by melting point, IR, 1H NMR, 13C NMR and elemental analysis. This method has some advantages with short reaction time, mild reaction condition, simple operation, high yields and with no chromatographic separation procedure. All the title compounds were evaluated for anticancer activities in vitro against HL-60 cell lines and Hela human cervical cartcinoma cell lines. The results showed that 4-(4'-bromophenylamino)-5-(2', 3'-dichlorophenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4k) and 4-(4'-bromo- phenylamino)-5-(4'-nitrophenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4l) exhibited high activity against HL-60 with IC50 values of (11.3±0.3) and (10.8±0.2) μmol/L, and 4-(4'-chlorophenylamino)-5-(3', 4', 5'-trimethoxyphenyl)- chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4g) and 4-(3'-chloro-4'-fluorophenylamino)-5-(3', 4', 5'-trimethoxy- phenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4h) exhibited high activity against Hela with IC50 value of (9.2±0.6) and (8.5±0.2) μmol/L.

Key words: pyranocoumarin fused primidine, cyanoenamine, synthesis, anticancer activity