Design, synthesis and biological evaluation of novel 4-(pyrrolo[2,3-d]pyrimidine-4-yloxy)benzamide derivatives as potential antitumor agents

被引：9

作者：

Zhang, Jianqing ^{[1
,2
]}

Xiong, Hehua ^{[3
]}

Yang, Feiyi ^{[2
]}

He, Jie ^{[2
]}

Chen, Ting ^{[4
]}

Fu, Dongxue ^{[4
]}

Zheng, Pengwu ^{[2
]}

Tang, Qidong ^{[1
,2
]}

机构：

[1] Wenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China

[2] Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China

[3] China Pharmaceut Univ, Dept Pharmaceut Anal, State Key Lab Nat Med, Key Lab Drug Qual Control & Pharmacovigilance, Nanjing 210009, Peoples R China

[4] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou 325035, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2021年 / 33卷

基金：

中国国家自然科学基金;

关键词：

Synthesis; 4-(Pyrrolo[2,3-d]pyrimidine-4-yloxy)benzamide; Inhibitors; Antitumor activity; SAR; KINASE INHIBITORS; CANCER CELLS; MET;

D O I：

10.1016/j.bmcl.2020.127740

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cancer is a major cause of death worldwide. Small molecule inhibitors have become a major therapeutic treatment for cancer. In this study, a series of novel 4-(pyrrolo[2,3-d]pyrimidine-4-yloxy)benzamide derivatives were designed, synthesized and evaluated for their antitumor activity against the A549, Hela and MCF-7 cell lines. Among them, the optimal compound 35 was found to possess excellent inhibitory activity against the A549, Hela and MCF-7 cell lines with IC50 values of 5.29 +/- 0.58, 3.72 +/- 0.91, and 9.23 +/- 0.56 mu M, which were superior to Golvatinib. The structure-activity relationship showed that the introduction of 7H-pyrrolo[2,3-d] pyrimidine along with the F atom of the central and terminal benzene was beneficial to the improvement of inhibitory activity of the target compounds. Besides, we took further study on the combined mode between compound 35 and c-Met kinase through molecular docking

引用

页数：6

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