Design, synthesis, and structure–activity relationships of pyrazole derivatives as potential FabH inhibitors

✍ Scribed by Peng-Cheng Lv; Juan Sun; Yin Luo; Ying Yang; Hai-Liang Zhu

• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 265 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.05.105

✦ Synopsis

Fatty acid biosynthesis is essential for bacterial survival. FabH, b-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Fifty-six 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives were synthesized and developed as potent inhibitors of FabH. This inhibitor class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 1-(5-(4-fluorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1 H-pyrazol-1-yl)ethanone (12) and 1-(5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone ( 13) were potent inhibitors of E. coli FabH.