The discovery of the potent aurora inhibitor MK-0457 (VX-680)

被引：90

作者：

Bebbington, David ^{[1
]}

Binch, Hayley ^{[1
]}

Charrier, Jean-Damien ^{[1
]}

Everitt, Simon ^{[1
]}

Fraysse, Damien ^{[1
]}

Golec, Julian ^{[1
]}

Kay, David ^{[1
]}

Knegtel, Ronald ^{[1
]}

Mak, Chau ^{[1
]}

Mazzei, Francesca ^{[1
]}

Miller, Andrew ^{[1
]}

Mortimore, Michael ^{[1
]}

O'Donnell, Michael ^{[1
]}

Patel, Sanjay ^{[1
]}

Pierard, Francoise ^{[1
]}

Pinder, Joanne ^{[1
]}

Pollard, John ^{[1
]}

Ramaya, Sharn ^{[1
]}

Robinson, Daniel ^{[1
]}

Rutherford, Alistair ^{[1
]}

Studley, John ^{[1
]}

Westcott, James ^{[1
]}

机构：

[1] Vertex Pharmaceut Europe Ltd, Abingdon OX14 4RY, Oxon, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 13期

关键词：

Aurora; Kinase inhibitor; SAR; KINASE INHIBITORS; ANTICANCER AGENTS; CANCER; FAMILY; ABL; MUTANT; CELLS;

D O I：

10.1016/j.bmcl.2009.04.136

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The identification of a novel series of Aurora kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modi. cation of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (VX-680) has been assessed in Phase II clinical trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) containing the T315I mutation. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3586 / 3592

页数：7

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