- Discovery of an Orally Available Diazabicyclooctane Inhibitor (ETX0282) of Class A, C, and D Serine β-Lactamases
-
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.
- 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)
-
- BETA-LACTAMASE INHIBITOR COMPOUNDS
-
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, 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 (I): or a pharmaceutically acceptable salt thereof, wherein the values of R1, R2, R3, R4, R5 and R6 are described herein.
- -
-
Page/Page column 107; 108
(2018/04/13)
-
- HETEROBICYCLIC COMPOUNDS AS BETA-LACTAMASE INHIBITORS
-
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.
- -
-
Page/Page column 46
(2013/10/22)
-
- O-Protected N-(2-Nitrophenylsulfonyl)hydroxylamines: Novel Reagents for the Synthesis of Hydroxamates
-
Preparative methods for novel O-protected N-(2-nitrophenylsulfonyl)hydroxylamines (8a-e) are described. Their versatility as intermediates en route to polyhydroxamates is examplified by the synthesis of a non-amide DFO analog 22.
- Reddy, Poreddy Amruta,Schall, Otto F.,Wheatley, James R.,Rosik, Leonard O.,McClurg, Joseph P.,Marshall, Garland R.,Slomczynska, Urszula
-
p. 1086 - 1092
(2007/10/03)
-
