1897-87-6Relevant academic research and scientific papers
N-C Axially Chiral Compounds with an ortho-Fluoro Substituent and Steric Discrimination between Hydrogen and Fluorine Atoms Based on a Diastereoselective Model Reaction
Iida, Asumi,Matsuoka, Mizuki,Hasegawa, Hiroshi,Vanthuyne, Nicolas,Farran, Daniel,Roussel, Christian,Kitagawa, Osamu
, p. 3169 - 3175 (2019)
The fluorine atom is the second smallest atom; nevertheless, the ortho-fluoro group may lead to stable N-aryl atropisomers when the steric demand of the flanking substituents is large enough. 2-Alkyl-3-(2-fluorophenyl)quinazolin-4-ones and 3-(2-fluorophen
Palladium-catalyzed four-component carbonylative synthesis of 2,3-disubstituted quinazolin-4(3H)-ones: Convenient methaqualone preparation
Peng, Jin-Bao,Geng, Hui-Qing,Wang, Wei,Qi, Xinxin,Ying, Jun,Wu, Xiao-Feng
, p. 10 - 13 (2018/07/03)
A palladium-catalyzed four-component carbonylative cyclization reaction for the synthesis of 2,3-disubstituted quinazolin-4(3H)-ones has been developed. A range of different 2,3-disubstituted quinazolin-4(3H)-one derivatives were prepared in moderate to good yields employing simple and readily accessible 2-iodoanilines, nitro compounds and acid anhydrides as the synthetic precursors. Mo(CO)6 acted both as a solid CO source and a reductant. Notably, methaqualone as a sedative and hypnotic medication can be prepared easily in 68% yield (4b) under our conditions as well.
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.
