2,4,5-Triphenylisothiazol-3(2H)-one 1,1-dioxides as inhibitors of human leukocyte elastase.
Date
2005
Authors
Gutschow, M.
Pietsch, M.
Themann, A.
Fahrig, J.
Schulze, B.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Enzyme Inhibition and Medicinal Chemistry, 2005; 20(4):341-347
Statement of Responsibility
Michael Gütschow, Markus Pietsch, Andrea Themann, Janine Fahrigand Bärbel Schulze
Conference Name
Abstract
A series of substituted 2,4,5-triphenylisothiazol-3(2H)-one 1,1-dioxides 9 was synthesized and investigated as inhibitors of human leukocyte elastase (HLE). All compounds were found to inhibit HLE in a time-dependent manner and most of them exhibited kobs/[I] values > 300 M− 1s− 1. The most potent 3-oxosultam of this series was 9l (kobs/[I] = 2440 M− 1s− 1). Kinetic investigations performed with 9g and different substrate concentrations did not allow to clearly distinguish between a competitive or noncompetitive mode of inhibition. A more complex interaction is supported by the failure of a linear dependency of kobs values on the inhibitor concentration.