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All 9 posts Subject: Synth/pharm data on methaqualone analogs (compil.) Please login to post Down

pHarmacist
(pHantasticant)
11-09-03 20:52
No 469827
User Picture       Synth/pharm data on methaqualone analogs (compil.)
(Rated as: excellent)

Synthesis and anticonvulsant activity of some new 2-substituted 3-aryl-4(3H)-quinazolinones
James F. Wolfe, Terry L. Rathman, Mark C. Sleevi, James A. Campbell, Thomas D. Greenwood
J. Med. Chem.; 1990; 33(1); 161-166 (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.

____ __ _

Synthesis of 3,4-Dihydro-4-oxoquinazoline Derivatives as Potential Anticonvulsants
Niteen A. Vaidya, C. H. Panos, A. Kite, W. Ben Iturrian, and C. DeWitt Blanton, Jr.
J. Med. Chem. 1983,26, 1422-1425 (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.

____ __ _

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... wink

2-Amino-3-cyanofurans as Precursors for Anthranilic Acid Derivatives
Nixon Jr, W. J.; Garland, J. T.; Blanton Jr, C. Dewitt
Synthesis; 1980, 56 (http://pharmacist-hive.tripod.com/aminocyanofurans.pdf)

____ __ _

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. Taylor
J. Med. Chem.; 1977; 20(3); 379-386 (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.
____ __ _

A survey of reported synthesis of methaqualone and some positional and structural isomers
Etienne F. van Zyl
Forensic 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, cool

http://www.bassdrive.com/BassDrive.m3u

Chimimanie
(Hive Bee)
11-09-03 23:54
No 469885
User Picture       Nice articles

Thank you friend. wink

I will study quaalude a bit... smile

Rhodium
(Chief Bee)
11-10-03 00:43
No 469897
      Condensing information

It's a lot better to collect all of the articles in one and the same post (as I took the liberty of doing for you), regardless if you were trying to fish for multiple karma points or not by posting them in five separate posts.

Condensing information is almost as important as collecting it.

pHarmacist
11-10-03 00:49
      regardless if you were trying to fish for...
(Rated as: off-topic)

Chimimanie
11-10-03 01:11
      Can a rating bee lost?
(Rated as: off-topic)

pHarmacist
11-10-03 01:13
      How exactly can a rating be lost?
(Rated as: off-topic)

Chimimanie
11-10-03 01:31
      yeah, try it
(Rated as: off-topic)

pHarmacist
11-10-03 01:58
      You are right, indeed, ownage!
(Rated as: off-topic)

Chimimanie
11-10-03 02:03
      Ahah
(Rated as: off-topic)

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	All 9 posts		Subject: Synth/pharm data on methaqualone analogs (compil.)		Please login to post		Down


		pHarmacist (pHantasticant) 11-09-03 20:52 No 469827				Synth/pharm data on methaqualone analogs (compil.) (Rated as: excellent)
						Synthesis and anticonvulsant activity of some new 2-substituted 3-aryl-4(3H)-quinazolinones James F. Wolfe, Terry L. Rathman, Mark C. Sleevi, James A. Campbell, Thomas D. Greenwood J. Med. Chem.; 1990; 33(1); 161-166 (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. ____ __ _ Synthesis of 3,4-Dihydro-4-oxoquinazoline Derivatives as Potential Anticonvulsants Niteen A. Vaidya, C. H. Panos, A. Kite, W. Ben Iturrian, and C. DeWitt Blanton, Jr. J. Med. Chem. 1983,26, 1422-1425 (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. ____ __ _ 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 Derivatives Nixon Jr, W. J.; Garland, J. T.; Blanton Jr, C. Dewitt Synthesis; 1980, 56 (http://pharmacist-hive.tripod.com/aminocyanofurans.pdf) ____ __ _ 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. Taylor J. Med. Chem.; 1977; 20(3); 379-386 (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. ____ __ _ A survey of reported synthesis of methaqualone and some positional and structural isomers Etienne F. van Zyl Forensic 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, http://www.bassdrive.com/BassDrive.m3u



		Chimimanie (Hive Bee) 11-09-03 23:54 No 469885				Nice articles
						Thank you friend. I will study quaalude a bit...



		Rhodium (Chief Bee) 11-10-03 00:43 No 469897				Condensing information
						It's a lot better to collect all of the articles in one and the same post (as I took the liberty of doing for you), regardless if you were trying to fish for multiple karma points or not by posting them in five separate posts. Condensing information is almost as important as collecting it.



		pHarmacist 11-10-03 00:49				regardless if you were trying to fish for... (Rated as: off-topic)



		Chimimanie 11-10-03 01:11				Can a rating bee lost? (Rated as: off-topic)



		pHarmacist 11-10-03 01:13				How exactly can a rating be lost? (Rated as: off-topic)



		Chimimanie 11-10-03 01:31				yeah, try it (Rated as: off-topic)



		pHarmacist 11-10-03 01:58				You are right, indeed, ownage! (Rated as: off-topic)



		Chimimanie 11-10-03 02:03				Ahah (Rated as: off-topic)

All 9 posts	End of thread	Top