Eduardo L. Setti

3,4-Disubstituted Azetidinones as Selective Inhibitors of the Cysteine Protease Cathepsin K. Exploring P2 Elements for Selectivity

A novel series of 3,4-disubstituted azetidinones based inhibitors of the cysteine protease cathepsin K (Cat K) has been identified. Although not optimized, some of these compounds show at least 100-fold selectivity against other cathepsins. The use of cyclic moieties as P2 elements has proven to be crucial to achieve a high degree of selectivity.

Studies on penam sulfones III. Synthesis and β-lactamase inhibitory activity of sodium (6R)-6-(α-hydroxybenzyl)-2β-methoxyiminomethyl-2α-methylpenam-3α-carboxylate 1,1-dioxide and sodium 2β-acyl-2α-methylpenam-3α-carboxylate 1,1-dioxide

Abstract The synthesis and in vitro synergies of (6R)-6-(α-hydroxybenzyl)-2β-methoxyiminomethyl-2α-methylpenam-3α-carboxylate 1,1-dioxide ( 4 ) and 2β-acyl-2α-methylpenam-3α-carboxylate 1,1-dioxide ( 15 ) are described. Compound 15 showed good in vitro synergy in combination with piperacillin and ceftazidime against chromosomally mediated class I cephalosporinase producing organisms including TEM, SHV, and OXA-type enzymes producing microorganisms.

Studies on monobactams II. Synthesis and β-lactamase inhibitory activity of 4α-methyl-3-[(thien-2-yl)-methylene]-2-azetidinone-1-sulfonate

Two monobactam derivatives, potassium 4α-methyl-(3E)-[(thien-2-yl)methylene]-2-azetidinone-1-sulfonate and its (3Z)-isomer, were prepared and evaluated for their β-lactamase inhibitory activities. These compounds were devoid of β-lactamase inhibitory activity.