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

doi:10.6023/cjoc201708027

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

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基于烯胺腈结构的吡喃香豆素并嘧啶类化合物的合成及抗肿瘤活性研究

黄新炜^a, 刘建利^b

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,E-mail:huangxinw@sina.com E-mail:huangxinw@sina.com
基金资助:
西安市科技计划（No.CXY1443WL13）及陕西省教育厅基金（No.15JK2145）资助项目.

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

Huang Xinwei^a, Liu Jianli^b

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 E-mail:huangxinw@sina.com
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).

1. Synthesis and Anticancer Activities of Novel Pyranocoumarin Fused Pyrimidine Based on Cyanoenamine.PDF(8163KB)

Abstract

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

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Huang Xinwei, Liu Jianli. Synthesis and Anticancer Activities of Novel Pyranocoumarin Fused Pyrimidine Based on Cyanoenamine[J]. Chin. J. Org. Chem., 2018, 38(5): 1233-1241.

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基于烯胺腈结构的吡喃香豆素并嘧啶类化合物的合成及抗肿瘤活性研究

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

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