858840-42-3Relevant articles and documents
Targeting Bacillosamine Biosynthesis in Bacterial Pathogens: Development of Inhibitors to a Bacterial Amino-Sugar Acetyltransferase from Campylobacter jejuni
De Schutter, Joris W.,Morrison, James P.,Morrison, Michael J.,Ciulli, Alessio,Imperiali, Barbara
, p. 2099 - 2118 (2017)
The glycoproteins of selected microbial pathogens often include highly modified carbohydrates such as 2,4-diacetamidobacillosamine (diNAcBac). These glycoconjugates are involved in host-cell interactions and may be associated with the virulence of medically significant Gram-negative bacteria. In light of genetic studies demonstrating the attenuated virulence of bacterial strains in which modified carbohydrate biosynthesis enzymes have been knocked out, we are developing small molecule inhibitors of selected enzymes as tools to evaluate whether such compounds modulate virulence. We performed fragment-based and high-throughput screens against an amino-sugar acetyltransferase enzyme, PglD, involved in biosynthesis of UDP-diNAcBac in Campylobacter jejuni. Herein we report optimization of the hits into potent small molecule inhibitors (IC50 300 nM). Biophysical characterization shows that the best inhibitors are competitive with acetyl coenzyme A and an X-ray cocrystal structure reveals that binding is biased toward occupation of the adenine subpocket of the AcCoA binding site by an aromatic ring.
Crystal engineering of cadmium coordination polymers decorated with nitro-functionalized thiophene-2,5-dicarboxylate and structurally related bis(imidazole) ligands with varying flexibility
Xue, Li-Ping,Li, Zhao-Hao,Ma, Lu-Fang,Wang, Li-Ya
, p. 6441 - 6449 (2015/08/24)
A new thiophene-2,5-dicarboxylic acid derivative, 3-nitro-thiophene-2,5-dicarboxylic acid (H2ntdc), was synthesized. Reaction of H2ntdc with cadmium diacetate dihydrate and structurally related bis(imidazole) ligands with varying flexibility gave rise to four new CPs, formulated as {[Cd(ntdc)(bmip)(H2O)](H2O)}n (1), {[Cd(ntdc)(bmib)](H2O)}n (2), [Cd(ntdc)(beip)]n (3) and [Cd(ntdc)(beib)]n (4) [bmip = 1,3-bis(2-methylimidazolyl)propane, bmib = 1,4-bis(2-methylimidazolyl)butane, beip = 1,3-bis(2-ethylimidazolyl)propane and beib = 1,4-bis(2-ethylimidazolyl)butane]. Moreover, a new compound {[Cd(ntc)2(bmib)](H2O)}n (5) (Hntc = 4-nitro-thiophene-2-carboxylic acid) involving in situ ligand synthesis was prepared. Structural analyses reveal that 1 features a two-dimensional (2D) 44-sql layer, and is further stacked via hydrogen bonding interactions to give a three-dimensional (3D) hydrogen-bonded architecture. 2 displays a 3,4-connected 3D network with ins type topology, which is composed of 2D hcb topological networks pillared by the bmib ligands. 3 exhibits a 3,5-connected 3D network with a (42·63·85)(42·6) topology. 4 possesses a 3-fold interpenetrating 3D net with a dmp topology. 5 can be described as a one-dimensional (1D) chain structure, and is further assembled into a 2D hydrogen-bonded 44sql layer. Factors that influence the structural assembly of 1-4, as well as the formation of 5 involving the in situ produced Hntc ligand, are discussed. Moreover, structure stabilities and photoluminescence properties of the complexes were also investigated.
PROLYL HYDROXYLASE INHIBITORS
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Page/Page column 15-16, (2010/07/10)
The invention described herein relates to certain 2,4-dioxo-1,2,3,4-tetrahydrothieno[3,2- d]pyrimidme-6-carboxamide derivatives of formula (I) which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.
PROLYL HYDROXYLASE INHIBITORS
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Page/Page column 14-15, (2010/04/03)
The invention described herein relates to certain 4-oxo-2-thioxo- 1,2,3,4- tetrahydrothienopyrimidine-6-carboxamide derivatives of formula (I) and (II); which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from
