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Synthesis of 8-substituted derivatives of the 2-deoxy analogue of 3-deoxy-beta-D-manno-2-octulopyranosonic acid (2-deoxy-beta-KDO) as inhibitors of 3-deoxy-D-manno-octulosonate cytidylyltransferase. 1989

B G Pring, and A M Jansson, and K Persson, and I Andersson, and I Gagner-Milchert, and K Gustafsson, and A Claesson
Department of Antibacterial Chemotherapy, Research and Development, Astra Alab AB, Södertälje, Sweden.

The 2-deoxy analogue of 3-deoxy-beta-D-manno-2-octulopyranosonic acid (2-deoxy-beta-KDO, 2) is a potent inhibitor of the enzyme 3-deoxy-D-manno-octulosonate cytidylyltransferase, which is involved in the biosynthesis of lipopolysaccharide, an essential component of the outer membrane of Gram-negative bacteria. Since compound 2 lacks antibacterial activity, a series of 8-substituted derivatives of 2 has been synthesized in an attempt to find enzyme inhibitors suitable for modification as antibacterials. Compounds 9, 11, and 13, in which the 8-hydroxy group of 2 is replaced by F, H, and NH2, respectively, were as potent inhibitors of the enzyme as 2, but were devoid of antibacterial activity, with the exception of the amino acid 13, which showed weak activity against some strains of Salmonella typhimurium.

UI MeSH Term Description Entries
D008050 Lipid A Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties.
D009713 Nucleotidyltransferases A class of enzymes that transfers nucleotidyl residues. EC 2.7.7. Nucleotidyltransferase
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001419 Bacteria One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive. Eubacteria
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013400 Sugar Acids MONOSACCHARIDES and other sugars that contain one or more carboxylic acid moieties. Acids, Sugar

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