- Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones
-
In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 μM and against Mycobacterium bovis AN5A below 15 μM but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox assay at the active concentration range. The structure activity study relation provided some insight in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was selected as the most promising member of the library with a MIC of 3.2 μM and a CC50 against MRC-5 of 67.4 μM.
- de Macedo, Maíra Bidart,Kimmel, Roman,Urankar, Damijana,Gazvoda, Martin,Peixoto, Antonio,Cools, Freya,Torfs, Eveline,Verschaeve, Luc,Lima, Emerson Silva,Ly?ka, Antonín,Mili?evi?, David,Klásek, Antonín,Cos, Paul,Kafka, Stanislav,Ko?mrlj, Janez,Cappoen, Davie
-
p. 491 - 500
(2017/07/10)
-
- Cu(i)-catalyzed chemical fixation of CO2 with 2-alkynylaniline into 4-hydroxyquinolin-2(1H)-one
-
A copper(i) catalyzed reaction of 2-alkynylaniline with CO2 using DBU as base to produce 4-hydroxyquinolin-2(1H)-one derivatives in moderate to good yield is presented. In this reaction, a unique bond cleavage pattern for CO2 was observed that one of the C-O double bonds of CO 2 was totally broken and rearranged into two moieties in the absence of the reductive reagent. This efficient reaction system showed the wide generality of substrates including nitro, bromo, cyano and methoxylcarbonyl groups. A possible mechanism containing isocyanate intermediate is proposed. This journal is the Partner Organisations 2014.
- Guo, Chun-Xiao,Zhang, Wen-Zhen,Liu, Si,Lu, Xiao-Bing
-
p. 1570 - 1577
(2014/06/09)
-
- Efficient preparation of 4-hydroxyquinolin-2(1 H)-one derivatives with silver-catalyzed carbon dioxide incorporation and intramolecular rearrangement
-
Although 4-hydroxyquinolin-2(1H)-one derivatives have attracted much attention due to their biological benefits, conventional reactions under harsh heat conditions must be employed to provide these key compounds. In the presence of a catalytic amount of s
- Ishida, Tomonobu,Kikuchi, Satoshi,Yamada, Tohru
-
p. 3710 - 3713
(2013/08/23)
-
- Oxidative Hydroxylation of Heterocyclic β-Dicarbonyl Compounds
-
3-Substituted 4-hydroxy-2-quinolones (1), 5-substituted barbituric acids (3) and 4-substituted pyrazolidine-2,4-diones were oxidized to yield the corresponding hydroxyderivatives 2,4 or 9, respectively. - Keywords: 5-Hydroxy-2,4,6-pyrimidine-triones; 4-Hy
- Stadlbauer, Wolfgang,Kappe, Thomas
-
p. 1005 - 1016
(2007/10/02)
-