| Autor: |
Cregge, R. J., Durham, S. L., Farr, R. A., Gallion, S. L., Hare, C. M., Hoffman, R. V., Janusz, M. J., Kim, H.-O., Koehl, J. R., Mehdi, S., Metz, W. A., Peet, N. P., Pelton, J. T., Schreuder, H. A., Sunder, S., Tardif, C. |
| Zdroj: |
Journal of Medicinal Chemistry; July 2, 1998, Vol. 41 Issue: 14 p2461-2480, 20p |
| Abstrakt: |
A series of P2-modified, orally active peptidic inhibitors of human neutrophil elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were designed using pentafluoroethyl ketone 1 as a model. Rational structural modifications were made at the P3, P2, and activating group (AG) portions of 1 based on structure−activity relationships (SAR) developed from in vitro (measured Ki) data and information provided by modeling studies that docked inhibitor 1 into the active site of HNE. The modeling-based design was corroborated with X-ray crystallographic analysis of the complex between 1 and porcine pancreatic elastase (PPE) and subsequently the complex between 1 and HNE. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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