Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray crystallographic analysis, and structure-activity relationships for a series of P2-modified, orally …

…, MJ Janusz, HO Kim, JR Koehl, S Mehdi…

Index: Cregge, Robert J.; Durham, Sherrie L.; Farr, Robert A.; Gallion, Steven L.; Hare, C. Michelle; Hoffman, Robert V.; Janusz, Michael J.; Kim, Hwa-Ok; Koehl, Jack R.; Mehdi, Shujaath; Metz, William A.; Peet, Norton P.; Pelton, John T.; Schreuder, Herman A.; Sunder, Shyam; Tardif, Chantal Journal of Medicinal Chemistry, 1998 , vol. 41, # 14 p. 2461 - 2480

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Citation Number: 54

Abstract

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 K i) data and information provided by modeling studies ...