4-(Pyrimidin-2-ylamino)benzamide Derivatives: Design, Synthesis, and Hedgehog Signaling Pathway Inhibition Study

被引：8
|
作者：
Zhang, Liandi [1 ,2 ]
Xin, Minhang [2 ,3 ]
Wen, Jun [2 ]
Tang, Feng [2 ]
Tu, Chongxing [2 ]
Shen, Han [2 ]
Wei, Ping [1 ]
机构：
[1] Nanjing Univ Technol, Coll Biotechnol & Pharmaceut Engn, Nanjing 211800, Jiangsu, Peoples R China
[2] Jiangsu Simcere Pharmaceut Co Ltd, Jiangsu Key Lab Mol Targeted Antitumor Drug Res, Nanjing 210042, Jiangsu, Peoples R China
[3] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Pharm, Xian 710061, Peoples R China
来源：
CHINESE JOURNAL OF ORGANIC CHEMISTRY | 2014年 / 34卷 / 07期
关键词：
hedgehog signaling pathway; 4-(pyrimidin-2-ylamino)benzamide; synthesis; inhibition;
D O I：
10.6023/cjoc201401004
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Hedgehog signaling pathway is a new therapeutic target for interventional cancer treatment. A novel series of 4-(pyrimidin-2-ylamino)benzamide derivatives were designed as hedgehog signaling pathway inhibitors based on our previously reported lead compound 1 and its structure activity relationship. Fourteen compounds were synthesized and the inhibitory effects on hedgehog signaling pathway of these compounds were evaluated. The results demonstrated that all the compounds presented good potency against hedgehog signaling pathway, and compound 8e was the most potent one with an IC50 value of 5.0 nmol.L-1, more potent than GDC-0449. Likewise, compound 8e displayed improved pharmacokinetic properties.
引用
收藏
页码：1407 / 1416
页数：10
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