83842-54-0Relevant articles and documents
Synthesis and characterization of a quinolinonic compound activating ATP-sensitive K+ channels in endocrine and smooth muscle tissues
Becker,Antoine,Nguyen,Rigo,Cosgrove,Barnes,Dunne,Pirotte,Lebrun
, p. 375 - 385 (2001)
1. Original quinolinone derivatives structurally related to diazoxide were synthesized and their effects on insulin secretion from rat pancreatic islets and the contractile activity of rat aortic rings determined. 2. A concentration-dependent decrease of insulin release was induced by 6-chloro-2-methylquinolin4(1H)-one (HEI 713). The average IC50 values were 16.9±0.8 μM for HEI 713 and 18.4±2.2μM for diazoxide. 3. HEI 713 increased the rate of 86Rb outflow from perifused pancreatic islets. This effect persisted in the absence of external Ca2+ but was inhibited by glibenclamide, a KATP channel blocker. Inside-out patch-clamp experiments revealed that HEI 713 increased KATP channel openings. 4. HEI 713 decreased 45Ca outflow, insulin output and cytosolic free Ca2+ concentration in pancreatic islets and islet cells incubated in the presence of 16.7 or 20 mM glucose and extracellular Ca2+. The drug did not affect the K+(50 mM)-induced increase in 45Ca outflow. 5. In aortic rings, the vasorelaxant effects of HEI 713, less potent than diazoxide, were sensitive to glibenclamide and to the extracellular K+ concentration. 6. The drug elicited a glibenclamide-sensitive increase in 86Rb outflow from perifused rat aortic rings. 7. Our data describe an original compound which inhibits insulin release with a similar potency to diazoxide but which has fewer vasorelaxant effects. 8. Our results suggest that, in both aortic rings and islet tissue, the biological effects of HEI 713 mainly result from activation of KATP channels ultimately leading to a decrease in Ca2+ inflow.
Green and Efficient Synthesis of 4-Heteryl-Quinolines and Their Antibacterial Evaluations
Bhupathi, Raja S.,Bandi, Madhu,Ch, Venkata Ramana Reddy,Rama Devi,Dubey
, p. 1236 - 1241 (2017/03/27)
A green and efficient synthesis of 4-heteryl-quinolines (9a, 9b, 9c, 9d), (10a, 10b, 10c, 10d) and (11a, 11b, 11c, 11d) has been described using PEG-600 as a green solvent. Initially, 4-chloro-2-methylquinolines (5a, 5b, 5c, 5d) on reaction with aromatic heterocyclic thiols (6), (7), and (8) using PEG-600 at 100°C for 30–40 min resulted in (9), (10), and (11) in good yields. Alternatively, (9), (10), and (11) could also be prepared in dimethylformamide using K2CO3 as base and tetrabutylammonium bromide as phase transfer catalyst at 100°C for 1–2 h. All the compounds were synthesized and characterized by IR, NMR, mass spectroscopy, and 13C NMR analysis. All synthesized compounds were screened for their antibacterial activity against clinical strains that include Gram-positive (Bacillus subtilis MTCC 121, staphylococcus aureus MLS-16 MTCC 2940, Micrococcus lutes MTCC 2470, and Staphylococcus aureus MTCC 96) and Gram-negative bacteria (Candida albicans MTCC 3017, Klebsiella planticola MTCC 530, Escherichia coli MTCC 739, and Pseudomonas aeruginosa MTCC 2453). The results revealed that compounds (9a, 9d, 10a, 10c, 11b, and 11d) exhibited significant antibacterial activity almost equal to the standard drug, that is, Ciprofloxacin.
Discovery, synthesis, and optimization of antimalarial 4(1 H)-quinolone-3-diarylethers
Nilsen, Aaron,Miley, Galen P.,Forquer, Isaac P.,Mather, Michael W.,Katneni, Kasiram,Li, Yuexin,Pou, Sovitj,Pershing, April M.,Stickles, Allison M.,Ryan, Eileen,Kelly, Jane Xu,Doggett, J. Stone,White, Karen L.,Hinrichs, David J.,Winter, Rolf W.,Charman, Susan A.,Zakharov, Lev N.,Bathurst, Ian,Burrows, Jeremy N.,Vaidya, Akhil B.,Riscoe, Michael K.
, p. 3818 - 3834 (2014/05/20)
The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone.
Microwave-assisted Synthesis of 2-methyl-4-quinolinones via combes synthesis catalyzed by acidic resin under solvent-free condition
Yuan, Shizhen,Zhang, Kehua,Xia, Jingjing
, p. 5535 - 5538 (2013/07/26)
A simple and efficient method for the synthesis of 2-methylquinolin-4(1H)- one derivatives using NKC-9-resin as reusable eco-friendly catalyst via Combes cyclization under solvent-free and microwave irradiation conditions is described. The quinolines were obtained in high yields and in short reaction times.
4-Substituted Thioquinolines and Thiazoloquinolines: Potent, Selective, and Tween-80 invitro Dependent Families of Antitubercular Agents with Moderate invivo Activity
Escribano, Jaime,Rivero-Hernandez, Cristina,Rivera, Hilda,Barros, David,Castro-Pichel, Julia,Perez-Herran, Esther,Mendoza-Losana, Alfonso,Angulo-Barturen, Inigo,Ferrer-Bazaga, Santiago,Jimenez-Navarro, Elena,Ballell, Lluis
, p. 2252 - 2263 (2012/04/23)
Two new families of closely related selective, non-cytotoxic, and potent antitubercular agents were discovered: thioquinolines and thiazoloquinolines. The compounds were found to possess potent antitubercular properties invitro, an activity that is dependent on experimental conditions of MIC determination (resazurin test and the presence or absence of Tween-80). To clarify the therapeutic potential of these compound families, a medicinal chemistry effort was undertaken to generate a lead-like structure that would enable murine efficacy studies and help elucidate the invivo implications of the invitro observations. Although the final compounds showed only limited levels of systemic exposure in mice, modest levels of efficacy invivo at nontoxic doses were observed. Two new families: In this work we identified two new classes of potent antitubercular agents. Synthesis and analysis of the pharmacological properties of several analogues led to the discovery of potent and selective derivatives invitro, with moderate invivo activity.
NaHSO4/SiO2: An efficient catalyst for the synthesis of β-enaminones and 2-methylquinolin-4(1H)-ones under solvent-free condition
Sapkal, Suryakant B.,Shelke, Kiran F.,Shingate, Bapurao B.,Shingare, Murlidhar S.
experimental part, p. 723 - 726 (2011/03/19)
An efficient and simplified protocol for NaHSO4/SiO2 catalyzed solvent-free synthesis of β-enaminone and 2-methylquinolin-4(1H)- one derivatives under microwave irradiation is described. A series of functionalized derivatives have been synthesized in shorter reaction times with moderate to good yields. The use of milder catalyst in non-conventional method offers significant advantages over conventional methods, such as higher selectivities, simplicity, solvent-free reaction and non-environmental polluting conditions.
Divergent route to access structurally diverse 4-quinolones via mono or sequential cross-couplings
Cross, R. Matthew,Manetsch, Roman
supporting information; experimental part, p. 8654 - 8657 (2011/03/20)
A divergent route was developed to access 3-iodo- and 6-chloro-3-iodo-4(1H) -quinolones for further elaboration via mono and/or sequential Suzuki-Miyaura cross-coupling to generate novel and medicinally important 4(1H)-quinolones. Copper- and palladium-ca
Endochin optimization: Structure-activity and structure-property relationship studies of 3-substituted 2-Methyl-4(1 H)-quinolones with antimalarial activity
Cross, R. Matthew,Monastyrskyi, Andrii,Mutka, Tina S.,Burrows, Jeremy N.,Kyle, Dennis E.,Manetsch, Roman
experimental part, p. 7076 - 7094 (2010/12/25)
Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC50 against erythrocytic stages of multidrug resistant W2 and TM90-C2B isolates of Plasmodium falciparum. Follow-up structure-activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure-property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC50 in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.
Synthesis of a quinolone library from ynones
Ward, Timothy R.,Turunen, Brandon J.,Haack, Torsten,Neuenswander, Benjamin,Shadrick, William,Georg, Gunda I.
experimental part, p. 6494 - 6497 (2011/02/24)
A library of 72 quinolones was synthesized from substituted anthranilic acids, using ynone intermediates. These masked β-dicarbonyl synthons allowed cyclization under milder conditions than previously reported quinolone syntheses.
Microwave-assisted solvent-free synthesis of 4-methyl-2-hydroxy- And 2-methyl-4-hydroxyquinolines
Nadaraj,Selvi, S. Thamarai
, p. 1203 - 1207 (2008/09/18)
Rapid and efficient microwave-assisted synthesis of 4-methyl-2-hydroxy- and 2-methyl-4-hydroxyquinolines from anilines and ethyl acetoacetate under different conditions is described.
