title: Solid-phase synthesis of quinolinone library.
abstract: Quinolinones have various biological activities, including antibacterial, anticancer, and antiviral properties. The 3-substituted amide quinolin-2(1H)-ones not only show antibacterial activity, but also act as immunomodulators, 5-HT4 receptor agonists, cannabinoid receptor inverse agonists, and AchE and, BuchE inhibitors. To investigate the potent biological activity of 3-substituted amide quinolin-2(1H)-ones, a large number of 3,5-amide substituted-2-oxoquinolinones were prepared by parallel solid-phase synthesis. The compound 5-amino-1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylic acid was loaded onto 4-formyl-3,5-dimethoxyphenoxy (PL-FDMP) resin by reductive amination with high efficiency. Various building blocks were attached to the 3 and 5 positions to yield 3,5-disubstituted-2-oxoquinolinones with high purity and good yield. The ability some of these compound to inhibit the release of IL-1β, a cytokine involved in the immune response was measured, and they showed about 50% inhibition at 10 μM.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST) , Gwangju 500-712, Republic of Korea.
authors.forename: Seung-Hwa
authors.initials: SH
authors.lastname: Kwak
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: So-Deok
authors.initials: SD
authors.lastname: Lee
authors.forename: Hyun
authors.initials: H
authors.lastname: You
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Hyojin
authors.initials: H
authors.lastname: Ko
mesh_terms: D066244:Proton Magnetic Resonance Spectroscopy; D015363:Quinolones / Q000138:chemical synthesis*; D060327:Solid-Phase Synthesis Techniques; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D015363:Quinolones
keywords: IL-1β; immune response; quinolinone; solid-phase synthesis