27255-72-7Relevant articles and documents
Novel Cephalosporin Conjugates Display Potent and Selective Inhibition of Imipenemase-Type Metallo-β-Lactamases
Tehrani, Kamaleddin H. M. E.,Wade, Nicola,Mashayekhi, Vida,Brüchle, Nora C.,Jespers, Willem,Voskuil, Koen,Pesce, Diego,Van Haren, Matthijs J.,Van Westen, Gerard J. P.,Martin, Nathaniel I.
, p. 9141 - 9151 (2021)
In an attempt to exploit the hydrolytic mechanism by which β-lactamases degrade cephalosporins, we designed and synthesized a series of novel cephalosporin prodrugs aimed at delivering thiol-based inhibitors of metallo-β-lactamases (MBLs) in a spatiotemporally controlled fashion. While enzymatic hydrolysis of the β-lactam ring was observed, it was not accompanied by inhibitor release. Nonetheless, the cephalosporin prodrugs, especially thiomandelic acid conjugate (8), demonstrated potent inhibition of IMP-type MBLs. In addition, conjugate 8 was also found to greatly reduce the minimum inhibitory concentration of meropenem against IMP-producing bacteria. The results of kinetic experiments indicate that these prodrugs inhibit IMP-type MBLs by acting as slowly turned-over substrates. Structure-activity relationship studies revealed that both phenyl and carboxyl moieties of 8 are crucial for its potency. Furthermore, modeling studies indicate that productive interactions of the thiomandelic acid moiety of 8 with Trp28 within the IMP active site may contribute to its potency and selectivity.
CEPHALOSPORIN-TYPE COMPOUNDS
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Paragraph 0134; 0135, (2017/12/09)
The present technology is directed to compounds, compositions, and methods related to the treatment of bacterial and fungal infections. The compounds are of Formula I or stereoisomers, tautomers, solvates, and/or pharmaceutically acceptable salts thereof. The present technology is especially well-suited for use in treating non-replicating Mycobacterium tuberculosis.
De-esterification process
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, (2008/06/13)
An efficient process for de-esterification has been provided for by application of special tetrahalogenides. By applying this process a new compound, viz. cefesone, and especially the E-isomer thereof, has been prepared.