2. Academic Validation
  3. Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors

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

Affiliation

  • 1 Department of Biology, Sunesis Pharmaceuticals, Inc., 395 Oyster Point Boulevard Suite 400, South San Francisco, CA 94080, USA. rfucini@sunesis.com
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.

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