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Published on: June 23, 2019
Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors
Raymond V Fucini1, Emily J Hanan, Michael J Romanowski
1Department of Biology, Sunesis Pharmaceuticals, Inc., 395 Oyster Point Boulevard Suite 400, South San Francisco, CA 94080, USA. rfucini@sunesis.com
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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