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2005
Isoxazole derivatives
R 0240
Isoxazole-3-hydroxamic Acid Derivatives as Peptide Deformylase Inhibitors and
Antibacterial Agents. — Title derivatives (V) and (VII) are identified as a
15- 120 Potential
new class of small, nonpeptidic inhibitors of peptide deformylase. These compounds
display inhibitory activity on the enzymes from E. coli and S. aureus, but show poor
antibacterial activity in Gram-negative strains. A molecular model suggests three key
interactions between the inhibitors and the enzyme binding site: i) bidendate coordination to the metal centre, ii) H-bond with Ile 44, and iii) hydrophobic interaction at P1'
position. — (CALI*, P.; NAERUM, L.; MUKHIJA, S.; HJELMENCRANTZ, A.;
Bioorg. Med. Chem. Lett. 14 (2004) 24, 5997-6000; Combio A/S, Frederiksberg,
DK-1800 Copenhagen, Den.; Eng.) — H. Hoennerscheid
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