Synthesis and structure-activity relationship of 2-arylamino-4-aryl-pyrimidines as potent PAK1 inhibitors

被引：13

作者：

Xu, Yong ^{[1
]}

Foulks, Jason M. ^{[1
]}

Clifford, Adrianne ^{[1
]}

Brenning, Benjamin ^{[1
]}

Lai, Shuping ^{[1
]}

Luo, Bai ^{[1
]}

Parnell, K. Mark ^{[1
]}

Merx, Shannon ^{[1
]}

McCullar, Michael V. ^{[1
]}

Kanner, Steven B. ^{[1
]}

Ho, Koc-Kan ^{[1
]}

机构：

[1] Astex Pharmaceut Inc, Dublin, CA 94568 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 14期

关键词：

PAK1; kinase; 2-Arylamino-4-aryl-pyrimidines; Colon cancer; Pak1; inhibitor; Bioisostere; CANCER-CELLS; P21-ACTIVATED KINASE; EXPRESSION; TARGET; AMPLIFICATION; MECHANISM; CARCINOMA; REVEALS;

D O I：

10.1016/j.bmcl.2013.05.059

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-Arylamino-4-aryl-pyrimidines were found to be potent inhibitors of PAK1 kinase. The synthesis and SAR are described. The incorporation of a bromide at the 5-position of the pyrimidine core and in combination with a 1,2-dimethylpiperazine pendant domain yielded a lead compound with potent PAK1 inhibition and anti-proliferative activity in various colon cancer cell lines. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4072 / 4075

页数：4