2,4,5-Triphenylisothiazol-3(2H)-one 1,1-dioxides as inhibitors of human leukocyte elastase |
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| Authors: | Michael Gütschow Markus Pietsch Andrea Themann Janine Fahrig Bärbel Schulze |
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| Affiliation: | 1. Poppelsdorf, University of Bonn, Pharmaceutical Institute, Kreuzbergweg 26, D-53115, Bonn, Germany;2. University of Leipzig, Institute of Organic Chemistry, Johannisallee 29, D-04103, Leipzig, Germany |
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| 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. |
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| Keywords: | Human leukocyte elastase 2,4,5-triphenylisothiazol-3(2H)-one 1,1-dioxides sultams inhibition |
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