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The powerful trypanocidal activity of certain phenanthridinium compounds was first demonstrated by Browning and his collaborators in 1938 (Browning, Morgan, Robb, and Walls, 1938;Walls, 1947a; Browning, 1949). This activity is highly specific against African bovine trypanosomiasis caused by T. congolense and T. vivax. A single dose is usually effective and, in spite of local irritant action and the occasional late toxic effects observed in some districts, several million doses have been given. The drugs have thus gained a place in the treatment of a disease for which radical cure was previously difficult to achieve.At the time the work described in this paper started it had been demonstrated (Walls, 1947b) that high trypanocidal activity in the phenanthridinium series is a property of quaternary salts containing a primary amino-group in the 7-and a phenyl group in the 9-position; the activity is much enhanced by the presence of a second primary amino-group, 2: 7-diamino-9-phenyl-10-methylphenanthridinium bromide (dimidium bromide) being particularly effective. Compounds with the amino-group in the 3-position are less active. Our work was designed to test these conclusions further, and if possible to extend them. The investigations fall into five main groups:(a) To establish whether the 7-position represents the optimum location for the first primary amino-group.(b) To determine the effect of variation of the 9-substituent and, in particular, whether the high activity of the 2: 7-diamino-compounds is associated with other 9-substituents than phenyl.(c) To determine the effect of modifying the primary amino-groups.(d) To determine the effect of alkoxyl groups. (e) To consider the relation between trypanocidal and antibacterial activity.

Summary1. Regression' equations were calculated relating the observed antimalarial potencies of arylamidinoureas to their predicted physicochemical properties. 2. A two-parameter equation was used to forecast the antimalarial activity of more arylamidinoureas. 3. Thirteen compounds of the predicted type were synthesized, and their observed antimalarial potencies compared with the forecasts. IntroductionAttempts to correlate biological activity quantitatively with physicochemical properties (reviewed by Tute, 1971) have usually been restricted to studies on completed series of compounds. In the present paper we describe an attempt to use regression equations based on approximate observations of the antimalarial activity of arylamidinoureas (Richards & Walls, unpublished observations) in order to forecast which new compounds in this series should be highly active. Thirteen of the new compounds were then synthesized and their observed biological activities compared with the forecasts.

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