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Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains of Escherichia coli. We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria. With the help of X-ray structures, this information was used to design inhibitors with activity on efflux-proficient, wild-type strains. Optimization of properties such as solubility, metabolic stability and serum protein binding resulted in compounds having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogens E. coli and Klebsiella pneumoniae. Other favorable properties of the series include a lack of pre-existing resistance in clinical isolates, and no loss of activity against strains expressing extended-spectrum-β-lactamase, metallo-β-lactamase, or carbapenemase-resistance genes. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance. [ABSTRACT FROM AUTHOR]

The article presents a study on synthetic protocols for the synthesis of some sulfonamides based on 2,3-dihydro-1 H-pyrrolo[3,4- c]pyridine. Topics discussed include preparation of pyrrolo[3,4-c]-pyrine derivatives containing oxo groups at definite positions of pyrrole part of the molecule, how 3-Oxypyrrolol[3,4-c]pyridines were prepared, and structures of synthesized compounds.

Abstract: The reaction of 8-bromoguanines with aryl and hetaryl stannanes in the presence of a palladium catalyst leads to the formation of the corresponding 8-aryl(hetaryl)guanines. It was found that the addition of triphenylarsine or triphenylbismuth strongly reduces the reaction time and increases product yields. [Copyright &y& Elsevier]

The title compound, C18H19N5O7S, can be considered as a synthetic analogue of nucleosides. The mol­ecule displays an anti conformation. The occurrence of N—H⋯O hydrogen bonds results in the formation of centrosymmetric dimers. The crystal packing is characterized by π–π stacking inter­actions between the purine systems. [ABSTRACT FROM AUTHOR]