Synthesis and central nervous system activity of quinazolones related to 2-methyl-3-(o-tolyl)-4(3H)-quinazolone (methaqualone)

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-fluoro...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1977-03, Vol.20 (3), p.379-386
Main Authors: Ager, I. R, Harrison, D. R, Kennewell, P. D, Taylor, J. B
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants - chemical synthesis
Central Nervous System - drug effects
Depression, Chemical
Male
Methaqualone - analogs & derivatives
Methaqualone - chemical synthesis
Methaqualone - pharmacology
Mice
Postural Balance - drug effects
Quinones - antagonists & inhibitors
Structure-Activity Relationship
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00213a013