| Autor: |
Cregge RJ; Hoechst Marion Roussel Inc., 2110 East Galbraith Road, Cincinnati, Ohio 45215, USA., Durham SL, Farr RA, Gallion SL, Hare CM, Hoffman RV, Janusz MJ, Kim HO, Koehl JR, Mehdi S, Metz WA, Peet NP, Pelton JT, Schreuder HA, Sunder S, Tardif C |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1998 Jul 02; Vol. 41 (14), pp. 2461-80. |
| DOI: |
10.1021/jm970812e |
| 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: |
MEDLINE |
| Externí odkaz: |
|
