埃罗替尼衍生物的合成及抗肿瘤活性

Synthesis and antitumor activities of erlotinib derivatives

目的:设计和合成出新的喹唑啉类化合物并研究其抗肿瘤活性。方法:3,4-二甲氧基苯甲酸乙酯经过醚化,再依次经过硝化、还原、环合得到4-氯-[6,7-二(2-甲氧基乙氧基)]-3H-喹唑啉-4-酮,最后氯代、与间氨基苯乙炔缩合、水解制得抗肿瘤药埃罗替尼,或者与氨基衍生物炔缩合、水解生成目标化合物。按MTT方法测定了目标化合物抗肿瘤活性。结果和结论:合成了8个埃罗替尼衍生物(8a～8h),其结构经核磁、质谱和红外光谱等数据确证。初步的抗肿瘤活性研究表明:在对人肺癌细胞A549的体外生长抑制作用上,所合成化合物对人肺癌细胞A549均具有一定程度的抑制作用,其中,化合物8a、8c和8h活性与吉非替尼和埃罗替尼相当。

Aim： To study the synthesis and antitumor activities of erlotinib derivatives. Methods： Erlotinib derivatives were synthesized from ethyl 3, 4-dimethoxybenzoate via etherification, nitrification, reduction, and then cyclization to afford 4-chloro-[ 6, 7-di（2-methoxyethoxy） quinazolin-4-one, which was finally subjected to chlorination and condensation with 3-aminophenylacetylene or other aminoderivatives. Percentage of inhibition on the antitumor growth was measured using MTT method. Results and Conclusion： Eight compounds of erlotinib derivatives （8a-8b） were synthesized, and their structures were identified by ^1H NMR, MS and IR. Preliminary antitumor activity testings showed that all of the compounds had the activities to different extents, and that compound 8a, 8c, 8h had activities to liver cancer cell line A549 that were approximately equivalent to that of erlotinib.