Download MendeleyDesign and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors
Rankovic, Z., Cai, J., Kerr, J., Fradera, X., Robinson, J., Mistry, A., Hamilton, E., McGarry, G., Andrews, F., Caulfield, W., Cumming, I., Dempster, M., Waller, J., Scullion, P., Martin, I., Mitchell, A., Long, C., Baugh, M., Westwood, P., Kinghorn, E., Bruin, J., Hamilton, W., Uitdehaag, J., van Zeeland, M., Potin, D., Saniere, L., Fouquet, A., Chevallier, F., Deronzier, H., Dorleans, C., Nicolai, E.(2010) Bioorg Med Chem Lett 20: 1524-1527
- PubMed: 20149657
- DOI: https://doi.org/10.1016/j.bmcl.2010.01.100
- Primary Citation of Related Structures:
3KW9, 3KWZ, 3KX1 - PubMed Abstract:
Morphing structural features of HTS-derived chemotypes led to the discovery of novel 2-cyano-pyrimidine inhibitors of cathepsin K with good pharmacokinetic profiles, for example, compound 20 showed high catK potency (IC(50)=4nM), >580-fold selectivity over catL and catB, and oral bioavailability in the rat of 52%.
Organizational Affiliation:
Schering-Plough Corporation, Newhouse, Lanarkshire, ML1 5SH Scotland, United Kingdom. zoran.rankovic@spcorp.com
