Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.

@article{Dunford2008StructureactivityRA,
  title={Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.},
  author={James E. Dunford and Aaron A. Kwaasi and Michael J Rogers and B. Lewis Barnett and Frank H. Ebetino and R. Graham G. Russell and Udo C. T. Oppermann and Kathryn L. Kavanagh},
  journal={Journal of medicinal chemistry},
  year={2008},
  volume={51 7},
  pages={2187-95}
}
The nitrogen-containing bisphosphonates (N-BPs) are the main drugs currently used to treat diseases characterized by excessive bone resorption. The major molecular target of N-BPs is farnesylpyrophosphate synthase. N-BPs inhibit the enzyme by a mechanism that involves time dependent isomerization of the enzyme. We investigated features of N-BPs that confer maximal slow and tight-binding by quantifying the initial and final K(i)s and calculating the isomerization constant K(isom) for many N-BPs… CONTINUE READING