1174020-63-3Relevant articles and documents
Diazabicyclooctane Functionalization for Inhibition of β-Lactamases from Enterobacteria
Bouchet, Flavie,Atze, Heiner,Fonvielle, Matthieu,Edoo, Zainab,Arthur, Michel,Ethève-Quelquejeu, Mélanie,Iannazzo, Laura
, p. 5257 - 5273 (2020)
Second-generation β-lactamase inhibitors containing a diazabicyclooctane (DBO) scaffold restore the activity of β-lactams against pathogenic bacteria, including those producing class A, C, and D enzymes that are not susceptible to first-generation inhibitors containing a β-lactam ring. Here, we report optimization of a synthetic route to access triazole-containing DBOs and biological evaluation of a series of 17 compounds for inhibition of five β-lactamases representative of enzymes found in pathogenic Gram-negative bacteria. A strong correlation (Spearman coefficient of 0.87; p = 4.7 × 10-21) was observed between the inhibition efficacy of purified β-lactamases and the potentiation of β-lactam antibacterial activity, indicating that DBO functionalization did not impair penetration. In comparison to reference DBOs, avibactam and relebactam, our compounds displayed reduced efficacy, likely due to the absence of hydrogen bonding with a conserved asparagine residue at position 132. This was partially compensated for by additional interactions involving certain triazole substituents.
Simple preparation method of Relebactam intermediate
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, (2019/07/04)
The invention discloses a simple preparation method of Relebactam intermediate, namely (2S,5R)-N-(1-protective group) piperidine-4-yl-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane - 2- formamide, (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl chloride is prepared from (2S, 5R) -5- benzyloxaminopiperidine -2- formic acid and phosgene, solid phosgene or diphosgene in a solventin the presence of an alkali and a catalyst by epoxidation and acylating chlorination reaction by a one-pot method, and the (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl chlorideis not separated and is directly subjected to amidation reaction with (1-protective group)-4-amino piperidine to obtain the (2S,5R)-N-(1-protective group) piperidine-4-yl-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane - 2- formamide. The method disclosed by the invention is simple in steps, cheap and easily available in raw materials, green and environment-friendly in process, low in cost, high in reaction atom economy, high in purity, yield and selectivity of the obtained intermediate, and beneficial to industrial production.
PROCESS FOR THE PREPARATION OF TERT-BUTYL 4-((2S,5R)-6-(BENZYLOXY)-7-OXO-1,6-DIAZABICYCLO[3.2.1]OCTANE-2-CARBOXAMIDO)PIPERIDINE-1-CARBOXYLATE AND ANALOGS THEREOF
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Page/Page column 20-22, (2016/06/28)
The present invention relates to processes for preparing compounds of Formula I. Such compounds include intermediates in the manufacture of 7-oxo-1,6- diazabicyclo[3.2.1 ]octane-2-carboxamide beta-lactamase inhibitors such as (2S,5R)-7-oxo-N- 5 piperidin-