Discovery of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of potent and selective checkpoint kinase 1 inhibitors.

@article{Tong2007DiscoveryO1,
  title={Discovery of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of potent and selective checkpoint kinase 1 inhibitors.},
  author={Yunsong Tong and Akiyo Claiborne and Kent D. Stewart and Chang Hee Park and Peter Kovar and Zehan Chen and Robert B Credo and Wen-zhen Gu and Stephen L Gwaltney and Russell A. Judge and Haiying Zhang and Saul H. Rosenberg and Hing Leung Sham and Thomas J Sowin and Nan-horng Lin},
  journal={Bioorganic & medicinal chemistry},
  year={2007},
  volume={15 7},
  pages={2759-67}
}
A new class of checkpoint kinase 1 (CHK-1) inhibitors bearing a 1,4-dihydroindeno[1,2-c]pyrazole core was developed after initial hits from high throughput screening. The efficient hit-to-lead process was facilitated by X-ray crystallography and led to potent inhibitors (<10nM) against CHK-1. X-ray co-crystal structures of bound inhibitors demonstrated that two sub-series of this class of compounds, exemplified by 21 and 41, exhibit distinctive hydrogen bonding patterns in the specificity… CONTINUE READING