Inhibition of human leukocyte elastase. 1. Inhibition by C-7-substituted cephalosporin tert-butyl esters

Publisher Website
Google Scholar
Abstract
Time-dependent inhibitors of the enzyme human leukocyte elastase have been developed based on the cephem nucleus. A series of cephalosporin tert-butyl esters has been examined, and the activity of these compounds has been found to be very sensitive to C-7 substituents, with small, .alpha.-oriented, electron-withdrawing groups showing greatest activity. Additionally, the oxidation state of the sulfur has been found to play a role in potency, with sulfones showing considerably greater activity than the corresponding sulfides or .beta.-sulfoxides. The .alpha.-sulfoxides were inactive.