375836-83-2

Upstream product

• 155473-89-5 6-mercapto-3,3-dimethyl-8-morpholin-4-yl-3,4-dihydro-1H-pyrano[3,4-c]pyridine-5-carbonitrile 
• 103-63-9 1-phenyl-2-bromoethane 
• 1194-16-7 2,2-dimethyltetrahydropyran-4-one 

Relevant academic research and scientific papers

Characterization of a novel pyranopyridine inhibitor of the AcrAB efflux pump of Escherichia coli

Members of the resistance-nodulation-division (RND) family of efflux pumps, such as AcrAB-TolC of Escherichia coli, play major roles in multidrug resistance (MDR) in Gram-negative bacteria. A strategy for combating MDR is to develop efflux pump inhibitors (EPIs) for use in combination with an antibacterial agent. Here, we describe MBX2319, a novel pyranopyridine EPI with potent activity against RND efflux pumps of the Enterobacteriaceae. MBX2319 decreased the MICs of ciprofloxacin (CIP), levofloxacin, and piperacillin versus E. coli AB1157 by 2-, 4-, and 8-fold, respectively, but did not exhibit antibacterial activity alone and was not active against AcrAB-TolC-deficient strains. MBX2319 (3.13 μM) in combination with 0.016 μg/ml CIP (minimally bactericidal) decreased the viability (CFU/ml) of E. coli AB1157 by 10,000-fold after 4 h of exposure, in comparison with 0.016 μg/ml CIP alone. In contrast, phenyl-arginine-β-naphthylamide (PAβN), a known EPI, did not increase the bactericidal activity of 0.016 μg/ml CIP at concentrations as high as 100 μM. MBX2319 increased intracellular accumulation of the fluorescent dye Hoechst 33342 in wild-type but not AcrAB-TolC-deficient strains and did not perturb the transmembrane proton gradient. MBX2319 was broadly active against Enterobacteriaceae species and Pseudomonas aeruginosa. MBX2319 is a potent EPI with possible utility as an adjunctive therapeutic agent for the treatment of infections caused by Gram-negative pathogens. Copyright

ANTIMICROBIAL POTENTIATORS

Novel compounds are disclosed having the structure of Formula I: wherein, n is an integer from 1 to 5; X is -CN, -F, -CI, -Br, -I, -N02; W is S, SO, S02, O, NH, or NR5; R5 is alkyl, aralkyl, alkenyl, or alkynyl;