Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors

  • Bioorg Med Chem Lett. 2008 Oct 15;18(20):5648-52. doi: 10.1016/j.bmcl.2008.08.095.
Raymond V Fucini  1 ,  Emily J Hanan ,  Michael J Romanowski ,  Robert A Elling ,  Willard Lew ,  Kenneth J Barr ,  Jiang Zhu ,  Joshua C Yoburn ,  Yang Liu ,  Bruce T Fahr ,  Junfa Fan ,  Yafan Lu ,  Phuongly Pham ,  Ingrid C Choong ,  Erica C VanderPorten ,  Minna Bui ,  Hans E Purkey ,  Marc J Evanchik ,  Wenjin Yang
Affiliations
  • 1. Department of Biology, Sunesis Pharmaceuticals, Inc., 395 Oyster Point Boulevard Suite 400, South San Francisco, CA 94080, USA. [email protected]
PMID: 18793847 DOI: 10.1016/j.bmcl.2008.08.095
Abstract

A series of 2-amino-pyrazolopyridines was designed and synthesized as Polo-like kinase (PLK) inhibitors based on a low micromolar hit. The SAR was developed to provide compounds exhibiting low nanomolar inhibitory activity of Plk1; the phenotype of treated cells is consistent with PLK1 inhibition. A co-crystal structure of one of these compounds with zPlk1 confirms an ATP-competitive binding mode.