Effect of the 7-amino substituent on the inhibitory potency of mechanism-based isocoumarin inhibitors for porcine pancreatic and human neutrophil elastases: a 1.85-. …

…, J Glinski, J Oleksyszyn, J Vijayalakshmi…

Index: Hernandez, Maria A.; Powers, James C.; Glinski, Jan; Oleksyszyn, Jozef; Vijayalakshmi, J.; Meyer, Edgar F. Journal of Medicinal Chemistry, 1992 , vol. 35, # 6 p. 1121 - 1129

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Citation Number: 27

Abstract

A series of new acyl, urea, and carbonate derivatives of 7-amino-4-chloro-3- methoxyisocoumarin were synthesized and evaluated as irreversible inhibitors of human neutrophil elastase (" E) and porcine pancreatic elastase (PPE). Inhibition of" E is duectly related to the hydrophobicity of the substituent on the% amino group. The N-Toe-Phe derivative (19) is the best HNE inhibitor with a second-order rate constant koh/[I]= 200000 ...