A contribution to the chemistry of antimalarials

Abstract

The aim of the present investigation was to obtain more information as to the relation between constitution (extended in the sense of configuration in certain instances) and anti-malarial activity in the acridine series and to prepare derivatives of other ring systems, which had not previously been tested for antimalarial activity.

Two bases which may resemble 2-amino-5-diethylamino-pentane in configuration were considered for condensations with 5-chloroacridines. The first, o-aminobenzyldiethylamine (I), was prepared by reduction of the nitro compound, obtained by the condensation of o-nitrobenzyl chloride with die thylamine. Four syntheses of the second base, 2-aminocyclohexyldiethylamine (II), were attempted but all were unsuccessful [diagram].

A third base, (3-diethylaminoethylamine, was prepared by the reduction of diethylamino-acetonitrile.

5-Chloroacridine (III) and 2:5-dichlero-7-methoxyacridine (IV) were prepared from the corresponding diphenylamine-2-carboxylio acids and 1:5-dichlero-9-methylacrldine (V) from the corresponding acridone.