227009-40-7Relevant academic research and scientific papers
Extending the β-lactamase-dependent prodrug armory: S- aminosulfeniminocephalosporins as dual-release prodrugs
Smyth, Timothy P.,O'Connor, Michael J.,O'Donnell, Michael E.
, p. 3132 - 3138 (1999)
Cephalosporins bearing an S-aminosulfenimine (R'(R'')NSN=) side chain at the 7-position are prototypic examples of a novel class of β-lactamase- dependent prodrug. Enzyme-catalyzed hydrolysis of the β-lactam ring in these structures triggers release of both the 3'-acetoxy group and the side chain sulfur-attached S-amino moiety as R'(R'')NH. This reactivity pattern should allow site-specific corelease of two distinct drug components from a cephalosporin, thereby providing a singular enhancement to the capacity of a cephalosporin as a prodrug nucleus; a key advantage of a dual-release prodrug is the potential to establish synergy between the coreleased structures. Areas for exploitation of this new structure type are antibody-directed enzyme prodrug therapy (ADEPT), which is a key emerging anticancer therapy, and the further development of site-specific-release prodrugs to combat the problem of β-lactamase-based resistance to antibiotics.
