Synthesis and antitumor activities of 4-(<i>N</i>-aryl)amino-6-long chain alkoxy pteridine derivatives

LIN Jin; WANG Xu; WANG Jian; XU Xiuzhi; CHEN Yaohao; LI Zhulai

doi:10.11665/j.issn.1000-5048.20180109

Journal of China Pharmaceutical University > 2018 > 49(1): 64-71. > DOI: 10.11665/j.issn.1000-5048.20180109

LIN Jin, WANG Xu, WANG Jian, XU Xiuzhi, CHEN Yaohao, LI Zhulai. Synthesis and antitumor activities of 4-(N-aryl)amino-6-long chain alkoxy pteridine derivatives[J]. Journal of China Pharmaceutical University, 2018, 49(1): 64-71. DOI: 10.11665/j.issn.1000-5048.20180109

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Synthesis and antitumor activities of 4-(N-aryl)amino-6-long chain alkoxy pteridine derivatives

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A series of 4-(N-aryl)amino-6-alkoxyl pteridine derivatives was designed and synthesized via the bioisostere principle using anti-cancer drugs with quinazoline cores as lead compounds. The proliferative inhibitory activities of the synthesized compounds against tumor cells A549, KG1a and HGC-27 were also performed by MTT assay. Using methyl 3-aminopyrazine-2-carboxylate as the starting material, 12 target compounds( 7a - 7l )were synthesized through six-step reaction, and characterized by ¹H NMR, ¹³C NMR and MS. It was showed that antitumor activity of pteridines with 2-chloro-5-nitro-anilino substituted in position 4 was more potent than that of others. The activity of compound 7b on A549 cells(IC₅₀=11. 55 μmol/L)was closely approximate to that of positive control gefitinib(IC₅₀=5. 95 μmol/L). IC₅₀ values of compound 7k on three cell lines were all close to those of gefitinib. A 2-chloro-5-nitro-anilino fragment was contained in preferred compounds which might be modified for further investigation.
- pteridine,
- quinazoline,
- synthesis,
- antitumor activity

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