Synthesis and anticonvulsant activity of some new 2-substituted 3-aryl-4(3H)-quinazolinonesJames F. Wolfe, Terry L. Rathman, Mark C. Sleevi, James A. Campbell, Thomas D. GreenwoodJ. Med. Chem.; 1990; 33(1); 161-166
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http://pharmacist-hive.tripod.com/2substquaalude.pdf)
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 61 and 8i, 8k, and 8p-r having a single ortho substituent on the 3-aryl group had the most promising anticonvulsant activity. Compounds 61 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 61 was ineffective against seizures induced by bicuculline, picrotoxin, and strychnine, while 8i showed some protection against picrotoxin-induced seizures.
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Synthesis of 3,4-Dihydro-4-oxoquinazoline Derivatives as Potential AnticonvulsantsNiteen A. Vaidya, C. H. Panos, A. Kite, W. Ben Iturrian, and C. DeWitt Blanton, Jr.J. Med. Chem. 1983,26, 1422-1425
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http://pharmacist-hive.tripod.com/quaalude3.pdf)
Abstract: Twenty-three substituted 3,4-dihydro-4-oxoquinazolines or 3,4-dihydro-4-oxoazaquinazolines have been synthesized utilizing 2-amino-3-cyano-4,5-dimethylfuran and methyl acrylate as precursors for synthesis of the required substituted anthranilates. Six additional azaquinazolones were synthesized from 2-aminonicotinic or 3-aminopicolinic acid for comparison studies. All compounds were evaluated in mice with the maximal electroshock (MES) seizure and pentylenetetrazol (sc Met) seizure threshold tests for potential anticonvulsant activity and in the rotorod test to evaluate neurotoxicity. Nine of the twenty-nine compounds in the series demonstrated anticonvulsant action. The azaquinazolones were found to possess the most significant activity.
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2-amino-3-cyano-4,5-dimethylfuran + Me-Acrylate -> Diels-Alder adduct -> anthranilate is a pretty damn sexy synthetic approach, nice illustration of the power of the absolutely genious Diels-Alder transformation... 
2-Amino-3-cyanofurans as Precursors for Anthranilic Acid DerivativesNixon Jr, W. J.; Garland, J. T.; Blanton Jr, C. DewittSynthesis; 1980, 56
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http://pharmacist-hive.tripod.com/aminocyanofurans.pdf)
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Synthesis and Central Nervous System Activity of Quinazolones Related to 2-Methyl-3-(o-tolyl)-4(3H)-quinazolone (Methaqualone)I. R. Ager, D. R. Harrison, P. D. Kennewell, and J. B. TaylorJ. Med. Chem.; 1977; 20(3); 379-386
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http://pharmacist.the-hive.tripod.com/qaaludeanal4.pdf)
Abstract: A number of derivatives of 2-methyl-3-(o-tolyl)-4(3H)-quinazolone bearing new substituents on the 2-methyl group have been synthesized. It was established that most substitutions at this position reduce or remove the CNS depressant activity of methaqualone. From the series prepared only the 2-fluoromethyl derivative or certain isothiouronium salts, which-could be hydrolyzed in vivo to the 2-mercaptomethyl derivative, showed activity of the same magnitude as methaqualone.
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A survey of reported synthesis of methaqualone and some positional and structural isomersEtienne F. van ZylForensic Science International 122 (2001) 142-149
(
http://pharmacist-hive.tripod.com/quaalude.pdf)
DOI:
doi:10.1016/S0379-0738(01)00484-4
Abstract: Methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone) is the illicit synthetic drug of choice amongst South African drug users. Historically police and forensic investigation has proven that all methaqualone seized by the South African Police Service originates from illicit manufacturing sites both inside, and outside South Africas borders. From a drug enforcement, and forensic point of view it is, thus, of utmost importance that the various synthetic routes available to the illicit "chemist" are fully documented and understood. This is a prerequisite for effective illicit laboratory investigation, as well as chemical and precursor monitoring. This paper gives a brief introduction to the current status with regard to methaqualone use and production in South Africa, as well as an extensive review of the synthesis of methaqualone and selected isomers reported since 1946. A table summarizing synthetic routes reported in 32 reference sources is provided.
Rh's archive is included in the refs section,
