1243143-35-2Relevant articles and documents
4-(3-Trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not N1 is critically important
Cai, Jiaqiang,Fradera, Xavier,Van Zeeland, Mario,Dempster, Maureen,Cameron, Kenneth S.,Bennett, D. Jonathan,Robinson, John,Popplestone, Lucy,Baugh, Mark,Westwood, Paul,Bruin, John,Hamilton, William,Kinghorn, Emma,Long, Clive,Uitdehaag, Joost C.M.
scheme or table, p. 4507 - 4510 (2010/10/21)
Using computer aided modelling studies, a new extended P2/S2 interaction was identified. This extended region can accommodate a variety of functional groups, such as aryls and basic amines. It was discovered that the N3 nitrogen of the pyrimidine-2-carbonitrile is critical for its cathepsin cysteine protease inhibition. N1 nitrogen also contributes to the inhibitory activity, but to a very limited degree. An 'in situ double activation' mechanism was proposed to explain these results.
