Author/Authors :
Raj N. Misra، نويسنده , , Hai-yun Xiao، نويسنده , , David K. Williams، نويسنده , , Kyoung S. Kim، نويسنده , , Songfeng Lu، نويسنده , , Kristen A. Keller، نويسنده , , Janet G. Mulheron، نويسنده , , Roberta Batorsky، نويسنده , , John S. Tokarski، نويسنده , , John S. Sack، نويسنده , , S. David Kimball، نويسنده , , Francis Y. Lee، نويسنده , , Kevin R. Webster، نويسنده ,
Abstract :
N-Aryl aminothiazoles 6–9 were prepared from 2-bromothiazole 5 and found to be CDK inhibitors. In cells they act as potent cytotoxic agents. Selectivity for CDK1, CDK2, and CDK4 was dependent of the nature of the N-aryl group and distinct from the CDK2 selective N-acyl analogues. The N-2-pyridyl analogues 7 and 19 showed pan CDK inhibitory activity. Elaborated analogues 19 and 23 exhibited anticancer activity in mice against P388 murine leukemia. The solid-state structure of 7 bound to CDK2 shows a similar binding mode to the N-acyl analogues.
