Chinese Journal of Organic Chemistry >
Synthesis and Anticancer Activities of Novel Pyranocoumarin Fused Pyrimidine Based on Cyanoenamine
Received date: 2017-08-14
Revised date: 2017-10-31
Online published: 2018-01-03
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.
Huang Xinwei , Liu Jianli . Synthesis and Anticancer Activities of Novel Pyranocoumarin Fused Pyrimidine Based on Cyanoenamine[J]. Chinese Journal of Organic Chemistry, 2018 , 38(5) : 1233 -1241 . DOI: 10.6023/cjoc201708027
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