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

Journal of Medicinal Chemistry
1990.0

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 atom 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.

Knowledge Graph

Similar Paper

Inhibition of human leukocyte elastase. 1. Inhibition by C-7-substituted cephalosporin tert-butyl esters
Journal of Medicinal Chemistry 1990.0
Oral absorption of cephalosproin antibiotics 2. Expanded structure-activity relationships of 7-arylacetamido-3-substituted cephalosporins
Journal of Medicinal Chemistry 1988.0
Simple phosphonic inhibitors of human neutrophil elastase
Bioorganic & Medicinal Chemistry Letters 2011.0
Semisynthetic cephalosporins. Synthesis and structure-activity relations of analogs with 7-acyl groups derived from 2-(cyanomethylthio)acetic acid or 2-[(2,2,2-trifluoroethyl)thio]acetic acid and their sulfoxides and sulfones
Journal of Medicinal Chemistry 1977.0
Cysteine Derivatives as Inhibitors for Carboxypeptidase A:  Synthesis and Structure−Activity Relationships
Journal of Medicinal Chemistry 2002.0
Semisynthetic cephalosporins. Synthesis and structure-activity relations of 7-sulfonylacetamido-3-cephem-4-carboxylic acids
Journal of Medicinal Chemistry 1976.0
Synthesis of cephems bearing olefinic sulfoxide side chains as potential β-lactamase inhibitors
Bioorganic & Medicinal Chemistry Letters 1996.0
Doxorubicin prodrug on the basis of tert -butyl cephalosporanate sulfones
Bioorganic & Medicinal Chemistry Letters 2004.0
Structure-activity relations in cephalosporins prepared from penicillins. 1. 7.beta.-Acylamino derivatives of 3-benzyl- and 3-(3-pyridylmethyl)ceph-3-em-4-carboxylic acids
Journal of Medicinal Chemistry 1977.0
The synthesis and evaluation of 6-alkylidene-2'β-substituted penam sulfones as β-lactamase inhibitors
Bioorganic & Medicinal Chemistry Letters 1999.0