Studies on biologically active halogenated compounds. II. Chemical modifications of 6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone and the CNS depressant activities of related compounds.

Abstract

A number of derivatives of 6-amino-2-fluoromethyl-3-(o-tolyl)-4 (3H)-quinazolinone (15), a potent muscle relaxant, have been prepared and screened in terms of the loss of righting reflex test and the rotating rod test in mice. Several derivatives with additional fluorine substitution or with repositioning of the fluorine atom exhibited high activities. Other structural modifications included acylation, carbamoylation, and alkoxycarbonylation of the 6-amino group, hydroxylation at the 3-tolyl group, and replacement of the fluorine atom at the 2-fluoromethyl group by oxygen, nitrogen, and sulfur nucleophiles ; these modifications all resulted in loss of activity.