Discovery of imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors

被引：36

作者：

Belanger, David B. ^{[1
]}

Curran, Patrick J. ^{[1
]}

Hruza, Alan ^{[2
]}

Voigt, Johannes ^{[2
]}

Meng, Zhaoyang ^{[1
]}

Mandal, Amit K. ^{[1
]}

Siddiqui, M. Arshad ^{[1
]}

Basso, Andrea D. ^{[3
]}

Gray, Kimberly ^{[3
]}

机构：

[1] Merck Res Labs, Dept Chem, Cambridge, MA 02141 USA

[2] Merck Res Labs, Dept Chem, Kenilworth, NJ 07033 USA

[3] Merck Res Labs, Dept Oncol, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 17期

关键词：

Aurora kinase inhibitors; Imidazo[1,2-a]pyrazine; EXPRESSION; CARCINOMA; OVEREXPRESSION;

D O I：

10.1016/j.bmcl.2010.07.008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and structure-activity relationships (SAR) of novel, potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors are described. The X-ray crystal structure of imidazo[1,2-a]pyrazine Aurora inhibitor 1j is disclosed. Compound 10i was identified as lead compound with a promising overall profile. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：5170 / 5174

页数：5

共 23 条

[1] Aurora kinases: shining lights on the therapeutic horizon? [J].

Andrews, PD .

ONCOGENE, 2005, 24 (32) :5005-5015

[2]

[Anonymous], [No title captured], Patent No. [0220189, 20040220189]

[3] Aurora kinase inhibitors: identification and preclinical validation of their biomarkers [J].

Carpinelli, Patrizia ;

Moll, Juergen .

EXPERT OPINION ON THERAPEUTIC TARGETS, 2008, 12 (01) :69-80

[4]

Cheung CHA, 2009, EXPERT OPIN INV DRUG, V18, P379, DOI [10.1517/13543780902806392 , 10.1517/13543780902806392]

[5] Advances in Aurora kinase inhibitor patents [J].

Coumar, Mohane Selvaraj ;

Cheung, Chun Hei Antonio ;

Chang, Jang-Yang ;

Hsieh, Hsing-Pang .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2009, 19 (03) :321-356

[6] Frequent overexpression of Aurora Kinase A in upper gastrointestinal adenocarcinornas correlates with potent antiapoptotic functions [J].

Dar, Altaf A. ;

Zaika, Alexander ;

Piazuelo, Maria B. ;

Correa, Pelayo ;

Koyama, Tatsuki ;

Belkhiri, Abbes ;

Washington, Kay ;

Castells, Antoni ;

Pera, Manuel ;

El-Rifai, Wael .

CANCER, 2008, 112 (08) :1688-1698

[7]

DeLano W.L., 2002, The PyMOL molecular graphics system

[8]

GUZI T, 2006, Patent No. 2006106023

[9] A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia [J].

Ikezoe, Takayuki ;

Yang, Jing ;

Nishioka, Chie ;

Tasaka, Taizo ;

Taniguchi, Ayuko ;

Kuwayama, Yoshio ;

Komatsu, Naoki ;

Bandobashi, Kentaro ;

Togitani, Kazuto ;

Koeffler, H. Phillip ;

Taguchi, Hirokuni .

MOLECULAR CANCER THERAPEUTICS, 2007, 6 (06) :1851-1857

[10] Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors [J].

Jung, FH ;

Pasquet, G ;

Lambert-van der Brempt, C ;

Lohmann, JJM ;

Warin, N ;

Renaud, F ;

Germain, H ;

De Savi, C ;

Roberts, N ;

Johnson, T ;

Dousson, C ;

Hill, GB ;

Mortlock, AA ;

Heron, N ;

Wilkinson, RW ;

Wedge, SR ;

Heaton, SP ;

Odedra, R ;

Keen, NJ ;

Green, S ;

Brown, E ;

Thompson, K ;

Brightwell, S .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (03) :955-970

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