359442-67-4Relevant articles and documents
Discovery of an Orally Available Diazabicyclooctane Inhibitor (ETX0282) of Class A, C, and D Serine β-Lactamases
Durand-Réville, Thomas F.,Comita-Prevoir, Janelle,Zhang, Jing,Wu, Xiaoyun,May-Dracka, Tricia L.,Romero, Jan Antoinette C.,Wu, Frank,Chen, April,Shapiro, Adam B.,Carter, Nicole M.,McLeod, Sarah M.,Giacobbe, Robert A.,Verheijen, Jeroen C.,Lahiri, Sushmita D.,Sacco, Michael D.,Chen, Yu,O'Donnell, John P.,Miller, Alita A.,Mueller, John P.,Tommasi, Rubén A.
supporting information, p. 12511 - 12525 (2020/12/17)
Multidrug resistant Gram-negative bacterial infections are an increasing public health threat due to rapidly rising resistance toward β-lactam antibiotics. The hydrolytic enzymes called β-lactamases are responsible for a large proportion of the resistance phenotype. β-Lactamase inhibitors (BLIs) can be administered in combination with β-lactam antibiotics to negate the action of the β-lactamases, thereby restoring activity of the β-lactam. Newly developed BLIs offer some advantage over older BLIs in terms of enzymatic spectrum but are limited to the intravenous route of administration. Reported here is a novel, orally bioavailable diazabicyclooctane (DBO) β-lactamase inhibitor. This new DBO, ETX1317, contains an endocyclic carbon-carbon double bond and a fluoroacetate activating group and exhibits broad spectrum activity against class A, C, and D serine β-lactamases. The ester prodrug of ETX1317, ETX0282, is orally bioavailable and, in combination with cefpodoxime proxetil, is currently in development as an oral therapy for multidrug resistant and carbapenem-resistant Enterobacterales infections.
HETEROBICYCLIC COMPOUNDS AS BETA-LACTAMASE INHIBITORS
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Page/Page column 46, (2013/10/22)
The present invention is directed to compounds which are beta-lactamase inhibitors. The compounds and their pharmaceutically acceptable salts, are useful in combination with beta-lactam antibiotics, or alone, for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant organisms. The present invention includes compounds according to formula (Ia): or a pharmaceutically acceptable salt thereof, wherein the values of R1, R 2, R 3 and R 4 are described herein.