Discovery of a novel class of 2-ureido thiophene carboxamide checkpoint kinase inhibitors

Checkpoint kinase-1 (Chk1, CHEK1) is a Ser/Thr protein kinase that mediates the cellular response to DNA-damage. A novel class of 2-ureido thiophene carboxamide urea (TCU) Chk1 inhibitors is described. Inhibitors in this chemotype were optimized for cellular potency and selectivity over Cdk1.

A series of thiophene carboxamide checkpoint kinase inhibitors (3) were discovered through HTS and optimized for cellular potency (12n).Figure optionsDownload as PowerPoint slide