Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity

A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure–activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.

In this paper we report on the optimization of the thieno[3,2-c]pyrazole series as inhibitors of the Aurora kinases to give a promising lead compound endowed with high potency in in vitro assays and active in vivo in the HL-60 xenograft tumor model.Figure optionsDownload as PowerPoint slide