1192651-49-2Relevant articles and documents
Preparation method of avibactam sodium
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, (2021/03/06)
The invention discloses a synthesis method of avibactam sodium. (2S,5R)-benzyloxyamino piperidine-2-ethyl formate oxalate (I) is used as an initial raw material; and the method comprises the followingsteps: reacting the raw material with a protecting group, carrying out carbonylation cyclization, carrying out hydrolysis of ester, ammoniating, sulfonating with a sulfur trioxide complex, salifyingwith an ammonium ion source, and salifying with a sodium salt to obtain avibactam sodium, and has the advantages of simple operation, easily controlled conditions, easy industrial production and wideapplication prospect.
Simple and convenient preparation method of avibatan intermediate
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, (2019/05/08)
The invention discloses a simple and convenient preparation method of an avibatan intermediate. The simple and convenient preparation method of the avibatan intermediate includes the steps that a typeIII compound is taken as a raw material, hydrolyzed under the alkaline condition, and then acidized to prepared a type IV compound, the obtained type IV compound and striphosgene or diphosgene are subjected to cyclic urea and acylating chlorination reactions simultaneously in the presence of an organic base and a catalyst, a type V compound is obtained, and a final product (II) is then obtained after amidation. According to the simple and convenient preparation method of the avibatan intermediate, the cyclic urea, acylating chlorination and amidation reactions are completed by a 'one pot method', and intermediate products do not need to be separated and purified; and raw materials are cheap and easy to get, the process is simple, operability is high, no special protective agent and carbonylation reagent are required, the reaction atom economical efficiency is high, the cost is low, the production process is environment friendly, the purity of the obtained product (II) is high, the yield is high, and cost reduction and environment-friendly production of an avibatan (I) is facilitated.
Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using β-Lactamase Inhibitors and β-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234
Papp-Wallace, Krisztina M.,Nguyen, Nhu Q.,Jacobs, Michael R.,Bethel, Christopher R.,Barnes, Melissa D.,Kumar, Vijay,Bajaksouzian, Saralee,Rudin, Susan D.,Rather, Philip N.,Bhavsar, Satish,Ravikumar, Tadiparthi,Deshpande, Prasad K.,Patil, Vijay,Yeole, Ravindra,Bhagwat, Sachin S.,Patel, Mahesh V.,Van Den Akker, Focco,Bonomo, Robert A.,Bonomo, Robert
, p. 4067 - 4086 (2018/05/23)
Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria possessing broad-spectrum β-lactamases. The design of novel β-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3, respectively), were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C, and D β-lactamases with unprecedented k2/K values against OXA carbapenemases. Compounds 1 and 2 acylated class A and C β-lactamses rapidly but not the tested OXAs. Compounds 1-3 formed highly stable acyl-complexes as demonstrated by mass spectrometry. Crystallography revealed that 1-3 complexed with KPC-2 adopted a "chair conformation" with the sulfate occupying the carboxylate binding region. The cefepime-2 and meropenem-3 combinations were effective in murine peritonitis and neutropenic lung infection models caused by MDR Acinetobacter baumannii. Compounds 1-3 are novel β-lactamase inhibitors that demonstate potent cross-class inhibition, and clinical studies targeting MDR infections are warranted.