939794-52-2Relevant academic research and scientific papers
Antibacterial Agents
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Page/Page column 45-46, (2009/01/20)
The invention provides compounds of formula (I) and salts thereof: R1-L-R2—B wherein R1, L, R2, and B have any of the values defined herein, as well as compositions comprising such compounds, and therapeutic methods comprising the administration of such compounds or salts. The compounds block siderophore production in bacteria and are useful as antibacterial agents.
5′-O-[(N-acyl)sulfamoyl]adenosines as antitubercular agents that inhibit MbtA: An adenylation enzyme required for siderophore biosynthesis of the mycobactins
Qiao, Chunhua,Gupte, Amol,Boshoff, Helena I.,Wilson, Daniel J.,Bennett, Eric M.,Somu, Ravindranadh V.,Barry III, Clifton E.,Aldrich, Courtney C.
, p. 6080 - 6094 (2008/09/18)
A study of the structure - activity relationships of 5′-O-[N- (salicyl)sulfamoyl]adenosine (6), a potent inhibitor of the bifunctional enzyme salicyl-AMP ligase (MbtA, encoded by the gene Rv2384) in Mycobacterium tuberculosis, is described, targeting the salicyl moiety. A systematic series of analogues was prepared exploring the importance of substitution at the C-2 position revealing that a hydroxy group is required for optimal activity. Examination of a series of substituted salicyl derivatives indicated that substitution at C-4 was tolerated. Consequently, a series of analogues at this position provided 4-fluoro derivative, which displayed an impressive MIC 99 of 0.098 μM against whole-cell M. tuberculosis under iron-limiting conditions. Examination of other heterocyclic, cycloalkyl, alkyl, and aminoacyl replacements of the salicyl moiety demonstrated that these nonconserative modifications were poorly tolerated, a result consistent with the fairly strict substrate specificities of related non-ribosomal peptide synthetase adenylation enzymes.
