摘要
以2,4-二羟基-6-氨基嘧啶、丙二腈和芳醛为原料,采用一锅法分别在加热与常温条件下合成了一系列吡啶并嘧啶类化合物,首次得到了副产物的晶体结构,证实此类反应过程中芳醛先于丙二腈缩合成不饱和二腈化合物.同时,对此反应催化剂的作用差别和动力学与热力学的作用差别进行了分析,探讨了芳构化的原因.结果证明,1,4-二氢吡啶的芳构化属于热力学作用的结果.所得化合物体外抗肿瘤活性测试实验结果显示,部分化合物的抗肿瘤活性优于阳性药五氟尿嘧啶和吉非替尼,为下一步抗肿瘤药物研究提供了很好的帮助.
A series of pyridopyrimidines are synthesized through a one-pot method under heating or ambient conditions using 2,4-dihydroxy-6-aminopyrimidine,malononitrile and aromatic aldehydes as the starting materials.Moreover,the crystal structure of the by-compound is obtained for the first time.It is proved that the aromatic aldehydes are condensed into unsaturated dinitriles compounds prior to malonitrile in this reaction.Meanwhile,the difference of the action of catalyst and the difference between kinetic and thermodynamic control over this reaction are investigated.The results indicate that the aromatization of 1,4-dihydropyridine is resulted from thermodynamic control.All of the compounds are tested for their in vitro antitumor activity against human cancer cell lines.The antiproliferative activity of some compounds is significantly better than that of 5-Fluorouracil and Gefitinib,these compounds will be used for the further study on antiproliferative agents.
作者
吴林韬
谢煜
韩春
景崤壁
汪清
WU Lintao;XIE Yu;HAN Chun;JING Xiaobi;WANG Qing(Department of Chemistry,Changzhi University,Changzhi 046011,China;School of Chemistry and Chemical Engineering,Yangzhou University,Yangzhou 225002,China)
出处
《扬州大学学报（自然科学版）》
CAS
北大核心
2021年第2期30-35,共6页
Journal of Yangzhou University：Natural Science Edition
基金
国家自然科学基金资助项目(21907010)
山西省应用基础研究计划资助项目(201801D221082)
山西省留学人员科技活动择优资助项目(20200025)。
