Prediction of relative potency of ketone protease inhibitors using molecular orbital theory

✍ Scribed by A.W. Edith Chan; Julian M.C. Golec

• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 474 KB
• Volume: 4
• Category: Article
• ISSN: 0968-0896
• DOI: 10.1016/0968-0896(96)00189-7

✦ Synopsis

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 ~ 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.