73283-22-4Relevant academic research and scientific papers
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.
2-Ketoalkyl-4(3H)-quinazolinones
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, (2008/06/13)
2-Ketoalkyl-4(3H)-quinazolinones of the formula STR1 wherein R1 is an aliphatic, cycloaliphatic or hydrocarbon aromatic group of 1-10 carbon atoms; A is divalent alkylene of 1 to 10 carbon atoms; R2 is an aliphatic, cycloaliphatic, hydrocarbon aromatic or heterocyclic group of 1-10 carbon atoms formed by condensing an acyl ester of the formula R2 COOR' which can be dissociated to form --COR2 and R'OH in which R' is the alcoholic portion of said ester; and R3 and R4 are each hydrogen, hydroxy, amino, halogen, trifluoromethyl, alkyl, alkoxy, alkylthio or alkylsulfonyl each of 1-4 carbon atoms, the substituents other than hydrogen when present being preferably in the 6- and/or 7-position of the quinazolinone nucleus provide compounds having useful activity as CNS depressants and anticonvulsants. A process is provided for preparing such compounds by ester condensation of a corresponding 2-alkyl-3-substituted-4(3H) quinazolinone with a condensable ester and excess sodium hydride in the presence of a strong ionization solvent such as refluxing 1,2-dimethoxyethane.
