Discovery and structure activity relationship study of novel indazole amide inhibitors for extracellular signal-regulated kinase1/2 (ERK1/2)

被引：12

作者：

Li, Lei ^{[1
]}

Liu, Feifei ^{[2
]}

Jin, Nan ^{[2
]}

Tang, Shuai ^{[2
]}

Chen, Zhuxi ^{[1
,2
]}

Yang, Xiaotong ^{[2
]}

Ding, Jian ^{[2
]}

Geng, Meiyu ^{[2
]}

Jiang, Lei ^{[1
]}

Huang, Min ^{[2
]}

Cao, Jianhua ^{[1
]}

机构：

[1] Green Valley Pharmaceut Co Ltd, Green Valley Res Inst, 421 Niudun Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 11期

关键词：

ERK1/2 kinase inhibitor; Indazole amide; Structure based drug design; MAP KINASE; ERK2; KINASE; CANCER; BRAF;

D O I：

10.1016/j.bmcl.2016.04.029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and optimization of a series of indazole amide based extracellular signal-regulated kinase inhibitors via structure/knowledge based drug design and kinase screen is reported. The optimized compounds demonstrate potent inhibition of ERK1/2 enzyme activity, growth of BRAF mutant HT29 cells and ERK signaling in HT29 cells. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：2600 / 2604

页数：5

共 15 条

[1]

[Anonymous], [No title captured]

[2] Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors [J].

Aronov, Alex M. ;

Baker, Christopher ;

Bemis, Guy W. ;

Cao, Jingrong ;

Chen, Guanjing ;

Ford, Pamella J. ;

Germann, Ursula A. ;

Green, Jeremy ;

Hale, Michael R. ;

Jacobs, Marc ;

Janetka, James W. ;

Maltais, Francois ;

Martinez-Botella, Gabriel ;

Namchuk, Mark N. ;

Straub, Judy ;

Tang, Qing ;

Xie, Xiaoling .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (06) :1280-1287

[3] Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control [J].

Aronov, Alex M. ;

Tang, Qing ;

Martinez-Botella, Gabriel ;

Bemis, Guy W. ;

Cao, Jingrong ;

Chen, Guanjing ;

Ewing, Nigel P. ;

Ford, Pamella J. ;

Germann, Ursula A. ;

Green, Jeremy ;

Hale, Michael R. ;

Jacobs, Marc ;

Janetka, James W. ;

Maltais, Francois ;

Markland, William ;

Namchuk, Mark N. ;

Nanthakumar, Suganthini ;

Poondru, Srinivasu ;

Straub, Judy ;

ter Haar, Ernst ;

Xie, Xiaoling .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (20) :6362-6368

[4] Tetrahydropyrrolo-diazepenones as inhibitors of ERK2 kinase [J].

Bagdanoff, Jeffrey T. ;

Jain, Rama ;

Han, Wooseok ;

Zhu, Shejin ;

Madiera, Ann-Marie ;

Lee, Patrick S. ;

Ma, Xiaolei ;

Poon, Daniel .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (18) :3788-3792

[5] Ligand efficient tetrahydro-pyrazolopyridines as inhibitors of ERK2 kinase [J].

Bagdanoff, Jeffrey T. ;

Jain, Rama ;

Han, Wooseok ;

Poon, Daniel ;

Lee, Patrick S. ;

Bellamacina, Cornelia ;

Lindvall, Mika .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (17) :3626-3629

[6] Discovery of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine inhibitors of Erk2 [J].

Blake, James F. ;

Gaudino, John J. ;

De Meese, Jason ;

Mohr, Peter ;

Chicarelli, Mark ;

Tian, Hongqi ;

Garrey, Rustam ;

Thomas, Allen ;

Siedem, Christopher S. ;

Welch, Michael B. ;

Kolakowski, Gabrielle ;

Kaus, Robert ;

Burkard, Michael ;

Martinson, Matthew ;

Chen, Huifen ;

Dean, Brian ;

Dudley, Danette A. ;

Gould, Stephen E. ;

Pacheco, Patricia ;

Shahidi-Latham, Sheerin ;

Wang, Weiru ;

West, Kristina ;

Yin, Jianping ;

Moffat, John ;

Schwarz, Jacob B. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (12) :2635-2639

[7]

BLAKE JF, 2013, WO, Patent No. [WO 2013130976, 2013130976]

[8]

Chaikuad A, 2014, NAT CHEM BIOL, V10, P853, DOI [10.1038/NCHEMBIO.1629, 10.1038/nchembio.1629]

[9]

Chen S., 2013, Patent, Patent No. [2013030138A1, 2013030138, WO2,013,030,138]

[10] MAP kinase signalling pathways in cancer [J].

Dhillon, A. S. ;

Hagan, S. ;

Rath, O. ;

Kolch, W. .

ONCOGENE, 2007, 26 (22) :3279-3290

← 1 2 →