4260-20-2Relevant academic research and scientific papers
Metal-free C-H methylation and acetylation of heteroarenes with PEG-400
Kudale, Vishal Suresh,Wang, Jeh-Jeng
supporting information, p. 3506 - 3511 (2020/06/25)
The generation of a methyl carbon source from renewable and cheap sources is challenging. Herein, we describe a novel and an efficient route for methylation and acetylation of aza-heteroarenes using PEG-400 under O2and TsOH·H2O for the first time by tuning the reaction conditions using a different set of starting materials. The key features of the current protocol are oxidative C-O and C-C bond scission under metal-free conditions with good functional group tolerance, and a broad substrate scope. The potential applicability of the designed methodology was demonstrated for the synthesis of central nervous system (CNS) depressant and anticonvulsant drug molecules by a one-pot strategy.
Deep eutectic solvent mediated synthesis of quinazolinones and dihydroquinazolinones: Synthesis of natural products and drugs
Ghosh, Suman Kr,Nagarajan, Rajagopal
, p. 27378 - 27387 (2016/04/04)
A mild and greener protocol was developed to synthesize substituted quinazolinones and dihydroquinazolinones via deep eutectic solvent (DES) mediated cyclization with a series of aliphatic, aromatic, and heteroaromatic aldehydes in good to excellent yields. This greener strategy was further utilised to synthesize various quinazolinone natural products and drugs.
Convenient synthesis of 2,3-disubstituted quinazolin-4(3H)-ones and 2-styryl-3-substituted quinazolin-4(3H)-ones: Applications towards the synthesis of drugs
Kumar, Dinesh,Jadhavar, Pradeep S.,Nautiyal, Manesh,Sharma, Himanshu,Meena, Prahlad K.,Adane, Legesse,Pancholia, Sahaj,Chakraborti, Asit K.
, p. 30819 - 30825 (2015/04/22)
Simple, convenient, and green synthetic protocols have been developed for the one pot synthesis of 2,3-disubstituted quinazolin-4(3H)-ones and 2-styryl-3-substituted quinazolin-4(3H)-ones under catalyst and solvent free conditions. The multicomponent reaction (3-MCR) involving isatoic anhydride, an amine, and orthoester afforded the 2,3-disubstituted quinazolin-4(3H)-ones in excellent yields under classical heating at 120 °C for 5 h or under microwave irradiation at 140°C for 20-30 min. The use of ammonium acetate instead of the amine provides the 2-substituted quinazolin-4(3H)-ones. The reactions are compatible with various substituted isatoic anhydrides, aryl/heteroaryl/alkyl/cycloalkyl amines, and orthoesters. The strategies are extended to the one pot tandem condensation involving isatoic anhydride, an amine, orthoester, and aldehyde to afford highly functionalized (E)-3-aryl/heteroaryl-2-styrylquinazolin/(2-(heteroaryl)vinyl)quinazolin-4(3H)-ones. The applications of the methodologies are demonstrated through the synthesis of various drugs which act on the central nervous system such as methaqualone, mebroqualone, mecloqualone, piriquialone, and diproqualone.
Atropisomeric quinazolin-4-one derivatives are potent noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists
Welch,Ewing,Huang,Menniti,Pagnozzi,Kelly,Seymour,Guanowsky,Guhan,Guinn,Critchett,Lazzaro,Ganong,DeVries,Staigers,Chenard
, p. 177 - 181 (2007/10/03)
Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure-activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity.
Synthesis and Anticonvulsant Activity of Some New 2-Substituted 3-Aryl-4(3H)-quinazolinones
Wolfe, James F.,Rathman, Terry L.,Sleevi, Mark C.,Campbell, James A.,Greenwood, Thomas D.
, p. 161 - 166 (2007/10/02)
A series of 4(3H)-quinazolinones structurally related to 2-methyl-3-o-tolyl-4(3H)-quinazolinone (methaqualone, 3) were synthesized and evaluated for anticonvulsant activity.Preliminary screening of these compounds revealed that 2--3-aryl-4(3H)-quinazolinones 6l and 8i, 8k, and 8p-r having a single ortho substituent on the 3-aryl group had the most promising anticonvulsant activity.Compounds 6l and 8i possessing 3-o-tolyl and 3-o-chlorophenyl groups, respectively, showed good protection against MES- and scMet-induced seizures, combined with relatively low neurotoxicity after intraperitoneal administration in mice.They also exhibited low toxicity in tests for determining the mean hypnotic dose (HD50) and the median lethal dose (LD50).Although these compounds were markedly more potent as anticonvulsants when administered orally in mice and rats, they were also more neurotoxic.This neurotoxicity was particularly acute in oral tests with rats. which resulted in marginal protective indices.In drug differentiation tests, compound 6l was ineffective against seizures induced by bicuculline, picrotoxin, and strychnine, while 8i showed some protection against picrotoxin-induced seizures.
