Design, synthesis and SAR of thienopyridines as potent CHK1 inhibitors
Lianyun Zhao1, Yingxin Zhang, Chaoyang Dai
1Department of Chemistry, Merck Research Laboratories, Cambridge, MA 02141, USA. lianyun.zhao@merck.com
Bioorganic & Medicinal Chemistry Letters
|November 16, 2010
Abstract:
A novel series of CHK1 inhibitors based on thienopyridine template has been designed and synthesized. These inhibitors maintain critical hydrogen bonding with the hinge and conserved water in the ATP binding site. Several compounds show single digit nanomolar CHK1 activities. Compound 70 shows excellent enzymatic activity of 1 nM.
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