The author of 《Heteroaryl Phosphonates as Noncovalent Inhibitors of Both Serine- and Metallocarbapenemases》 were Pemberton, Orville A.; Jaishankar, Priyadarshini; Akhtar, Afroza; Adams, Jessie L.; Shaw, Lindsey N.; Renslo, Adam R.; Chen, Yu. And the article was published in Journal of Medicinal Chemistry in 2019. Application In Synthesis of 3,5-Dibromoaniline The author mentioned the following in the article:
Gram-neg. pathogens expressing serine β-lactamases (SBLs) and metallo-β-lactamases (MBLs), especially those with carbapenemase activity, threaten the clin. utility of almost all β-lactam antibiotics. Here we describe the discovery of a heteroaryl phosphonate scaffold that exhibits noncovalent cross-class inhibition of representative carbapenemases, specifically the SBL KPC-2 and the MBLs NDM-1 and VIM-2. The most potent lead, compound 16, exhibited low nM to low μM inhibition of KPC-2, NDM-1, and VIM-2. Compound 16 potentiated imipenem efficacy against resistant clin. and laboratory bacterial strains expressing carbapenemases while showing some cytotoxicity toward human HEK293T cells only at concentrations above 100μg/mL. Complex structures with KPC-2, NDM-1, and VIM-2 demonstrate how these inhibitors achieve high binding affinity to both enzyme classes. These findings provide a structurally and mechanistically new scaffold for drug discovery targeting multidrug resistant Gram-neg. pathogens and more generally highlight the active site features of carbapenemases that can be leveraged for lead discovery. The experimental part of the paper was very detailed, including the reaction process of 3,5-Dibromoaniline(cas: 626-40-4Application In Synthesis of 3,5-Dibromoaniline)
3,5-Dibromoaniline(cas: 626-40-4) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Application In Synthesis of 3,5-Dibromoaniline
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary