Author/Authors :
Raymond V. Fucini، نويسنده , , Emily J. Hanan، نويسنده , , Michael J. Romanowski، نويسنده , , Robert A. Elling and David K. Wilson، نويسنده , , Willard Lew، نويسنده , , Kenneth J. Barr، نويسنده , , Jiang Zhu، نويسنده , , Joshua C. Yoburn، نويسنده , , Yang Liu، نويسنده , , Bruce T. Fahr، نويسنده , , Junfa Fan، نويسنده , , Yafan Lu، نويسنده , , Phuongly Pham، نويسنده , , Ingrid C. Choong، نويسنده , , Erica C. VanderPorten، نويسنده , , Minna Bui، نويسنده , , Hans E. Purkey، نويسنده , , Marc J. Evanchik، نويسنده , , Wenjin Yang، نويسنده ,
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.
Keywords :
SAR , kinase inhibitor , Polo-like kinase (Plk) , 2-Amino-pyrazolopyridine
