In 2017,Spaulding, Andrew; Takrouri, Khuloud; Mahalingam, Pornachandran; Cleary, Dillon C.; Cooper, Harold D.; Zucchi, Paola; Tear, Westley; Koleva, Bilyana; Beuning, Penny J.; Hirsch, Elizabeth B.; Aggen, James B. published 《Compound design guidelines for evading the efflux and permeation barriers of Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole cell Gram-negative activity》.Bioorganic & Medicinal Chemistry Letters published the findings.Application In Synthesis of 6-Bromopyridin-3-amine The information in the text is summarized as follows:
Previously the authors reported the results from an effort to improve Gram-neg. antibacterial activity in the oxazolidinone class of antibiotics via a systematic medicinal chem. campaign focused entirely on C-ring modifications. In that series the authors set about testing if the efflux and permeation barriers intrinsic to the outer membrane of Escherichia coli could be rationally overcome by designing analogs to reside in specific property limits associated with Gram-neg. activity: (i) low MW (<400), (ii) high polarity (clogD7.4 <1), and (iii) zwitterionic character at pH 7.4. Indeed, the authors observed that only analogs residing within these limits were able to overcome these barriers. Herein the authors report the results from a parallel effort where the authors explored structural changes throughout all three rings in the scaffold for the same purpose. Compounds were tested against a diagnostic MIC panel of Escherichia coli and Staphylococcus aureus strains to determine the impact of combining structural modifications in overcoming the OM barriers and in bridging the potency gap between the species. The results demonstrated that distributing the charge-carrying moieties across two rings was also beneficial for avoidance of the outer membrane barriers. Importantly, anal. of the structure-permeation relationship (SPR) obtained from this and the prior study indicated that in addition to MW, polarity, and zwitterionic character, having ≤4 rotatable bonds is also associated with evasion of the OM barriers. These combined results provide the medicinal chemist with a framework and strategy for overcoming the OM barriers in GNB in antibacterial drug discovery efforts. The experimental part of the paper was very detailed, including the reaction process of 6-Bromopyridin-3-amine(cas: 13534-97-9Application In Synthesis of 6-Bromopyridin-3-amine)
6-Bromopyridin-3-amine(cas: 13534-97-9) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.Application In Synthesis of 6-Bromopyridin-3-amine