Prediction of relative potency of ketone protease inhibitors using molecular orbital theory.
Molecular orbital calculations were carried out on a series of model ketonic protease inhibitors. A comparison of the LUMO energy of the ketones in a variety of model heterocyclic ketone protease inhibitors shows a correlation with the electrophilicity of the carbonyl, and the sigma 1 experimental data. It is also observed that the more negative charge on the nitrogen atom in the heterocyclic ring the greater its potential as a hydrogen bond acceptor. The results of this study provide a simple means of predicting relative inhibitor potency and is therefore of use both to medicinal chemists designing protease inhibitors and in QSAR studies.
Chan
A W
AW
Hoechst Marion Roussel, Covingham, Swindon, U.K.
Golec
J M
JM
D000465:Algorithms; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*
D007659:Ketones; D011480:Protease Inhibitors