In the case of quaternary compounds of the styryl quinoline series and of the analogous benzthiazole derivatives a powerful trypanocidal effect
in vivo
has been shown to depend on the presence in the substance of a free basic group in one of the nuclei, and anacylamino (especially acetyl) or urethane group in the other, and also on the styryl linkage—each playing a definite part in contributing to the action (Browning, Cohen, Ellingworth and Gulbransen, 1929, 1931). This is exemplified by 2(
p
-aminostyryl)-6 acetylamino quinoline methochloride (No. 8), 2(
p
-dimethylamino styryl)-6 acetylamino quinoline methochloride (No. 25), 2(
p
-acetylamino)-6 dimethylamino quinoline methochloride (No. 90) and 2(
p
-dimethylamino styryl) quinolyl (6) urethane (Me) methochloride (No. 125). The effect of acetylation of the amino group parallels that discovered by Ehrlich and his co-workers in the case of
p
-amino phenyl arsinic acid. Gough and King (1930) have recently made the important observation that in the latter series the introduction of an amide group converts the therapeutically inactive carboxylic and sulphonic acids into active compounds. Accordingly, the effect of substituting a carboxylamide group for the acylamino in compounds of the type of No. 25 and its anil analogue (No. 62) has been investigated. In addition, the position of the carboxylamide group has been varied. These substances were further examined for antiseptic action, the results being shown in the table.
Trypanocidal properties
have been tested on
T. brucei
infections in mice as in previous work. The striking observation has been made that only those compounds with the carboxylamide group in the 6 position are therapeutically active, the anils being only slightly less effective than the styryl analogues (
cf
. Nos. 410, 409 and 385, 403). This contrasts with what is found in the acetylamino derivatives, since the styryl compounds of the latter are highly active as compared with the corresponding anils. The carboxy-ethylamides (420, 419) are more toxic and less trypanocidal than the corresponding amides and methylamides.
Synthetic Studies in Quinoline Series. V