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

Abstract

Several derivatives of 2-methyl-3-(o-tolyl)-4(3H)-quinazolone bearing new substituents on the 2-methyl group were synthesized. Most substitutions at this position reduced or removed 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 [in mice].