25509-06-2

Upstream product

• 118-92-3 anthranilic acid 
• 525-76-8 2-methyl-4-oxo-3,1-benzoxazine 
• 608-31-1 2,6-Dichloroaniline 
• 89-52-1 o-acetylamino-benzoic acid 

Downstream Products

• 123382-23-0 3-(2,6-Dichloro-phenyl)-2-(2-oxo-2-pyridin-4-yl-ethyl)-3H-quinazolin-4-one 
• 96911-44-3 3-(2,6-Dichloro-phenyl)-2-[(E)-2-(4-methoxy-phenyl)-vinyl]-3H-quinazolin-4-one 
• 96911-50-1 2-[1,2-Dibromo-2-(4-methoxy-phenyl)-ethyl]-3-(2,6-dichloro-phenyl)-3H-quinazolin-4-one 

Relevant academic research and scientific papers

Atropisomeric quinazolin-4-one derivatives are potent noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists

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

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.