1121-31-9Relevant articles and documents
A Cephalosporin Prochelator Inhibits New Delhi Metallo-β-lactamase 1 without Removing Zinc
Jackson, Abigail C.,Zaengle-Barone, Jacqueline M.,Puccio, Elena A.,Franz, Katherine J.
, p. 1264 - 1272 (2020)
Antibacterial drug resistance is a rapidly growing clinical threat, partially due to expression of β-lactamase enzymes, which confer resistance to bacteria by hydrolyzing and inactivating β-lactam antibiotics. The increasing prevalence of metallo-β-lactamases poses a unique challenge, as currently available β-lactamase inhibitors target the active site of serine β-lactamases but are ineffective against the zinc-containing active sites of metallo-β-lactamases. There is an urgent need for metallo-β-lactamase inhibitors and antibiotics that circumvent resistance mediated by metallo-β-lactamases in order to extend the utility of existing β-lactam antibiotics for treating infection. Here we investigated the antibacterial chelator-releasing prodrug PcephPT (2-((((6R,7R)-2-carboxy-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]-oct-2-en-3-yl)methyl)thio) pyridine 1-oxide) as an inhibitor of New Delhi metallo-β-lactamase 1 (NDM-1). PcephPT is an experimental compound that we have previously shown inhibits growth of β-lactamase-expressing E. coli using a mechanism that is dependent on both copper availability and β-lactamase expression. Here, we found that PcephPT, in addition to being a copperdependent antibacterial compound, inhibits hydrolysis activity of purified NDM-1with an IC50 of 7.6 ìM without removing zinc from the active site and restores activity of the carbapenem antibiotic meropenem against NDM-1-producing E. coli. This work demonstrates that targeting a metal-binding pharmacophore to β-lactamase-producing bacteria is a promising strategy for inhibition of both bacterial growth and metallo-β-lactamases.
A Simple and Efficient Method for the Preparation of Heterocyclic N-Oxide
Zhong, Ping,Guo, Sheng-Rong,Song, Cai-Sheng
, p. 247 - 253 (2007/10/03)
Pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,4-dimethylpyridine, 2,6-dimethylpyridine, quinoline, isoquinoline and 2-chloropyridine are readily oxidized to their N-oxides with a solution of trichloroisocyanuric acid, acetic acid, sodium acetate and water in acetonitrile and methylene dichloride in 78%-90% yields.
Process for the manufacture of 2-mercapto pyridine-1-oxides
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, (2008/06/13)
A process for the manufacture of 2-mercaptopyridine-1-oxides and zinc salts thereof, comprising the steps of oxidizing a 2-acetylaminopyridine with peracetic acid in an inert solvent to give a 2-acetamidopyridine-1-oxide, cleaving the acetyl group with mineral acid to give a 2-aminopyridine-1-oxide, diazotizing the 2-aminopyridine-1-oxide and treating the diazonium salt with hydrochloric acid to give a 2-chloropyridine-1-oxide, treating the latter with a sulfhydryl-donor to give a 2-mercaptopyridine-1-oxide, and optionally treating the latter with a zinc salt to make the 2:1 zinc salt of the 2-mercaptopyridine-1-oxide. The resulting zinc salts are useful in anti-dandruff preparations.
