3KW9

Design 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 Search on PubMed
• 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%.

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Organizational Affiliation: 

Schering-Plough Corporation, Newhouse, Lanarkshire, ML1 5SH Scotland, United Kingdom. zoran.rankovic@spcorp.com