-transparent.png){kind=logo}
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-[2-oxo-2-(4-pyridyl)ethyl]-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.
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
August 1994,
Arzneimittel-Forschung,
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
May 1998,
Journal of medicinal chemistry,
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
January 1980,
Polish journal of pharmacology and pharmacy,
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
May 1992,
Arzneimittel-Forschung,
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
April 1994,
Archiv der Pharmazie,
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
December 1988,
Die Pharmazie,
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
May 1957,
Svensk farmaceutisk tidskrift,
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
January 1999,
Farmaco (Societa chimica italiana : 1989),
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
January 2024,
Turkish journal of chemistry,
J F Wolfe, and
T L Rathman, and
M C Sleevi, and
J A Campbell, and
T D Greenwood
October 2000,
European journal of medicinal chemistry,
