Progress against Escherichia coli with the Oxazolidinone Class of Antibacterials: Test Case for a General Approach To Improving Whole-Cell Gram-Negative Activity was written by Takrouri, Khuloud;Cooper, Harold D.;Spaulding, Adnrew;Zucchi, Paula;Koleva, Bilyana;Cleary, Dillon C.;Tear, Westley;Beuning, Penny J.;Hirsch, Elizabeth B.;Aggen, James B.. And the article was included in ACS Infectious Diseases in 2016.Name: 2-Bromo-4-hydroxybenzonitrile This article mentions the following:
Novel antibacterials with activity against the Gram-neg. bacteria associated with nosocomial infections, including Escherichia coli and other Enterobacteriaceae, are urgently needed due to the increasing prevalence of multidrug-resistant strains. A major obstacle that has stalled progress on nearly all small-mol. classes with potential for activity against these species has been achieving sufficient whole-cell activity, a difficult challenge due to the formidable outer membrane and efflux barriers intrinsic to these species. Using a set of compound design principles derived from available information relating physicochem. properties to Gram-neg. entry or activity, we synthesized and evaluated a focused library of oxazolidinone analogs, a currently narrow spectrum class of antibacterials active only against Gram-pos. bacteria. In this series, we have explored the effectiveness for improving Gram-neg. activity by identifying and combining beneficial structural modifications in the C-ring region. We have found polar and/or charge-carrying modifications that, when combined in hybrid C-ring analogs, appear to largely overcome the efflux and/or permeability barriers, resulting in improved Gram-neg. activity. In particular, those analogs least effected by efflux and the permeation barrier had significant zwitterionic character. In the experiment, the researchers used many compounds, for example, 2-Bromo-4-hydroxybenzonitrile (cas: 82380-17-4Name: 2-Bromo-4-hydroxybenzonitrile).
2-Bromo-4-hydroxybenzonitrile (cas: 82380-17-4) belongs to nitriles. There has been no report on the microbial biosynthesis of nitriles and the physiological function of such enzymes, nor was it not even known whether aliphatic and aromatic nitriles are biological compounds or just petrochemicals. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.Name: 2-Bromo-4-hydroxybenzonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts