Phenylimidazole derivatives as specific inhibitors of bacterial enoyl-acyl carrier protein reductase FabK.
Bacterial enoyl-acyl carrier protein (ACP) reductases (FabI and FabK) catalyze the final step in each cycle of bacterial fatty acid biosynthesis and are attractive targets for the development of new antibacterial agents. Here, we report the development of novel FabK inhibitors with antibacterial activity against Streptococcus pneumoniae. Based on structure-activity relationship (SAR) studies of our screening hits, we have developed novel phenylimidazole derivatives as potent FabK inhibitors.
Ozawa
Tomohiro
T
Medicinal Chemistry Research Laboratories, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
Kitagawa
Hideo
H
Yamamoto
Yasuo
Y
Takahata
Sho
S
Iida
Maiko
M
Osaki
Yumi
Y
Yamada
Keiko
K
D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology*; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
D004791:Enzyme Inhibitors; D007093:Imidazoles; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)