Non-nucleoside inhibitors of BasE, an adenylating enzyme in the siderophore biosynthetic pathway of the opportunistic pathogen Acinetobacter baumannii was written by Neres, Joao;Engelhart, Curtis A.;Drake, Eric J.;Wilson, Daniel J.;Fu, Peng;Boshoff, Helena I.;Barry, Clifton E.;Gulick, Andrew M.;Aldrich, Courtney C.. And the article was included in Journal of Medicinal Chemistry in 2013.Application In Synthesis of Methyl 6-bromo-1H-pyrrolo[2,3-b]pyridine-4-carboxylate The following contents are mentioned in the article:
Siderophores are small-mol. iron chelators produced by bacteria and other microorganisms for survival under iron limiting conditions such as found in a mammalian host. Siderophore biosynthesis is essential for the virulence of many important Gram-neg. pathogens including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. We performed high-throughput screening against BasE, which is involved in siderophore biosynthesis in A. baumannii, and identified 6-phenyl-1-(pyridin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid 15. Herein we report the synthesis, biochem., and microbiol. evaluation of a systematic series of analogs of the HTS hit 15. Analog 67 is the most potent analog with a KD of 2 nM against BasE. Structural characterization of the inhibitors with BasE reveals that they bind in a unique orientation in the active site, occupying all three substrate binding sites, and thus can be considered as multisubstrate inhibitors. These results provide a foundation for future studies aimed at increasing both enzyme potency and antibacterial activity. This study involved multiple reactions and reactants, such as Methyl 6-bromo-1H-pyrrolo[2,3-b]pyridine-4-carboxylate (cas: 1190315-53-7Application In Synthesis of Methyl 6-bromo-1H-pyrrolo[2,3-b]pyridine-4-carboxylate).
Methyl 6-bromo-1H-pyrrolo[2,3-b]pyridine-4-carboxylate (cas: 1190315-53-7) belongs to pyridine derivatives. Pyridine’s the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C鈥揌 in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.Application In Synthesis of Methyl 6-bromo-1H-pyrrolo[2,3-b]pyridine-4-carboxylate