Structure-based design, synthesis, and biological evaluation of potent and selective macrocyclic checkpoint kinase 1 inhibitors.

@article{Tao2007StructurebasedDS,
  title={Structure-based design, synthesis, and biological evaluation of potent and selective macrocyclic checkpoint kinase 1 inhibitors.},
  author={Zhi-Fu Tao and Le Wang and Kent D. Stewart and Zehan Chen and Wendy Gu and Mai-Ha Bui and Philip J. Merta and Haiying Zhang and Peter Kovar and Eric Arthur Johnson and Chang Hee Park and Russell A. Judge and Saul H. Rosenberg and Thomas J Sowin and Nan-horng Lin},
  journal={Journal of medicinal chemistry},
  year={2007},
  volume={50 7},
  pages={1514-27}
}
Based on the crystallographic analysis of a urea-checkpoint kinase 1 (Chk1) complex and molecular modeling, a class of macrocyclic Chk1 inhibitors were designed and their biological activities were evaluated. An efficient synthetic methodology for macrocyclic ureas was developed with Grubbs metathesis macrocyclization as the key step. The structure-activity relationship studies demonstrated that the macrocyclization retains full Chk1 inhibition activity and that the 4-position of the phenyl… CONTINUE READING