Synthesis and Antitumor Activities of Novel Pyrimidine Derivatives

化学工业与工程

Chemcial Industry and Engineering

2020, Vol. 37

Issue (3) :31-38 DOI: 10.13353/j.issn.1004.9533.20191512

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Synthesis and Antitumor Activities of Novel Pyrimidine Derivatives

Liu Luxian^1,2, Zhou Xueqin^1,2,3, Liu Dongzhi^1,2,3, Wang Tianyang², Li Wei^1,2,3

1. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China;
2. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China;
3. Tianjin Engineering Research Center of Functional Fine Chemicals, Tianjin 300350, China

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Abstract Structural modification of NVP-TAE684 was based on the reported ALK kinase inhibitor. Compound 1 was introduced into the nitrogen heterocycle pyrazine by amination to obtain compound 2, Boc group was then removed to give amine intermediates (3). Two pyrazine modified pyrimidine derivatives (7a, 7b) were finally obtained through palladium-catalyzed C-N coupling reactions of compound 3 (3a, 3b) and electrophilic reagent 6. Intermediates 2, 3 and the target compounds 7 have not been reported in other literature. The structures of all six novel compounds have been characterized by ¹H NMR, ¹³C NMR and HRMS-ESI. MTT method was employed to investigate the in vitro inhibition activities of 7a or 7b against non-small cell lung cancer NCI-H460 and NCI-H520. The results indicate that 7a and 7b show good inhibition activities and 7a shows the IC₅₀ value of 52.10±0.10 nM against NCI-H460.

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	Liu Luxian
	Zhou Xueqin
	Liu Dongzhi
	Wang Tianyang
	Li Wei

Keywords： ALK kinase inhibitors； pyrimidine； synthesis； antitumor activity

Received 2019-05-20;

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Liu Luxian, Zhou Xueqin, Liu Dongzhi, Wang Tianyang, Li Wei.Synthesis and Antitumor Activities of Novel Pyrimidine Derivatives[J] Chemcial Industry and Engineering, 2020,V37(3): 31-38

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