13067-94-2Relevant articles and documents
Synthesis and structure-activity relationships of quinolinone and quinoline-based P2X7 receptor antagonists and their anti-sphere formation activities in glioblastoma cells
Kwak, Seung-Hwa,Shin, Seungheon,Lee, Ji-Hyun,Shim, Jin-Kyoung,Kim, Minjeong,Lee, So-Deok,Lee, Aram,Bae, Jinsu,Park, Jin-Hee,Abdelrahman, Aliaa,Müller, Christa E.,Cho, Steve K.,Kang, Seok-Gu,Bae, Myung Ae,Yang, Jung Yoon,Ko, Hyojin,Goddard, William A.,Kim, Yong-Chul
, p. 462 - 481 (2018)
Screening a compound library of quinolinone derivatives identified compound 11a as a new P2X7 receptor antagonist. To optimize its activity, we assessed structure-activity relationships (SAR) at three different positions, R1, R2 and R3, of the quinolinone scaffold. SAR analysis suggested that a carboxylic acid ethyl ester group at the R1 position, an adamantyl carboxamide group at R2 and a 4-methoxy substitution at the R3 position are the best substituents for the antagonism of P2X7R activity. However, because most of the quinolinone derivatives showed low inhibitory effects in an IL-1β ELISA assay, the core structure was further modified to a quinoline skeleton with chloride or substituted phenyl groups. The optimized antagonists with the quinoline scaffold included 2-chloro-5-adamantyl-quinoline derivative (16c) and 2-(4-hydroxymethylphenyl)-5-adamantyl-quinoline derivative (17k), with IC50 values of 4 and 3 nM, respectively. In contrast to the quinolinone derivatives, the antagonistic effects of the quinoline compounds (16c and 17k) were paralleled by their ability to inhibit the release of the pro-inflammatory cytokine, IL-1β from LPS/IFN-γ/BzATP-stimulated THP-1 cells (IC50 of 7 and 12 nM, respectively). In addition, potent P2X7R antagonists significantly inhibited the sphere size of TS15-88 glioblastoma cells.
Discovery of a new antileishmanial hit in 8-nitroquinoline series
Paloque, Lucie,Verhaeghe, Pierre,Casanova, Magali,Castera-Ducros, Caroline,Dumetre, Aurelien,Mbatchi, Litaty,Hutter, Sebastien,Kraiem-M'Rabet, Manel,Laget, Michele,Remusat, Vincent,Rault, Sylvain,Rathelot, Pascal,Azas, Nadine,Vanelle, Patrice
, p. 75 - 86 (2012)
A series of nitrated 2-substituted-quinolines was synthesized and evaluated in vitro toward Leishmania donovani promastigotes. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Thus, a very promising antileishmanial hit molecule was identified (compound 21), displaying an IC50 value of 6.6 μM and CC 50 values ≥ 100 μM, conferring quite good selectivity index to this molecule, in comparison with 3 drug-compounds of reference (amphotericin B, miltefosine and pentamidine). Compound 21 also appears as an efficient in vitro antileishmanial molecule against both Leishmania infantum promastigotes and the intracellular L. donovani amastigotes (respective IC50 = 7.6 and 6.5 μM). Moreover, hit quinoline 21 does not show neither significant antiplasmodial nor antitoxoplasmic in vitro activity and though, presents a selective antileishmanial activity. Finally, a structure-activity relationships study enabled to define precisely the antileishmanial pharmacophore based on this nitroquinoline scaffold: 2-hydroxy-8-nitroquinoline.
Effects of the Distance between Radical Sites on the Reactivities of Aromatic Biradicals
Ding, Duanchen,Jiang, Hanning,Ma, Xin,Nash, John J.,Kentt?maa, Hilkka I.
supporting information, p. 8415 - 8428 (2020/10/02)
Coupling of the radical sites in isomeric benzynes is known to hinder their radical reactivity. In order to determine how far apart the radical sites must be for them not to interact, the gas-phase reactivity of several isomeric protonated (iso)quinoline-and acridine-based biradicals was examined. All the (iso)quinolinium-based biradicals were found to react slower than the related monoradicals with similar vertical electron affinities (i.e., similar polar effects). In sharp contrast, the acridinium-based biradicals, most with the radical sites farther apart than in the (iso)quinolinium-based systems, showed greater reactivities than the relevant monoradicals with similar vertical electron affinities. The greater distances between the two radical sites in these biradicals lead to very little or no spin-spin coupling, and no suppression of radical reactivity was observed. Therefore, the radical sites can still interact if they are located on adjacent benzene rings and only after being separated further than that does no coupling occur. The most reactive radical site of each biradical was experimentally determined to be the one predicted to be more reactive based on the monoradical reactivity data. Therefore, the calculated vertical electron affinities of relevant monoradicals can be used to predict which radical site is most reactive in the biradicals.
