Identification of novel, potent and selective inhibitors of Polo-like kinase 1

  • Bioorg Med Chem Lett. 2012 Jan 15;22(2):1247-50. doi: 10.1016/j.bmcl.2011.11.052.
Shaoqing Chen  1 ,  David Bartkovitz ,  Jianping Cai ,  Yi Chen ,  Zhi Chen ,  Xin-Jie Chu ,  Kang Le ,  Nam T Le ,  Kin-Chun Luk ,  Steve Mischke ,  Goli Naderi-Oboodi ,  John F Boylan ,  Tom Nevins ,  Weiguo Qing ,  Yingsi Chen ,  Peter M Wovkulich
Affiliations
  • 1. Discovery Chemistry, Hoffmann-La Roche Inc., Pharma Research & Early Development, Small Molecule Research, 340 Kingsland Street, Nutley, NJ 07110, United States. [email protected]
PMID: 22172702 DOI: 10.1016/j.bmcl.2011.11.052
Abstract

A series of pyrimidodiazepines was identified as potent Polo-like kinase 1 (PLK1) inhibitors. The synthesis and SAR are discussed. The lead compound 7 (RO3280) has potent inhibitory activity against PLK1, good selectivity against Other Kinases, and excellent in vitro cellular potency. It showed strong antitumor activity in xenograft mouse models.

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