The Selection of Arylamidinourea Antimalarials by Their Predicted Physicochemical Properties

Abstract

I A small group of arylamidinoureas for which the predicted physicochemical properties were widely spaced and uncorrelated was selected for study. 2 The antimalarial activity of each compound was measured against three species of plasmodium. Three corresponding regression equations were calculated relating the potency of each compound to its predicted physicochemical properties. 3 The potency of further test compounds was forecast for each species, by using the corresponding regression equation. These forecasts were compared with the measured activity of the test compounds, and were better than would be expected by chance. 4 It is suggested that only a few compounds in a series need be studied initially in order to derive regression equations with worthwhile predictive properties, if the compounds are selected according to appropriate criteria.

The physicochemical approach to drug design and discovery (QSAR)

“…Most, but not all, of the examples of good predictions realized via QSARarerathermodest uptonow. [Kimetal., 1979;Griecoetal., 1979;Hanschetal., 1977;Hansch, 1977;Bell and Roblin, 1942;Jorgensen and Reid, 1%5;Fuller et al, 1978;Beasley and Purcell, 1%9;Seydel and Wempe, 1971;Desmarchelier et al, 1973;Martinet al, 1973;Cousse et al, 1973;Bass et al, 1974;Neely et al, 1974;Martin and Biel, 1974;Cranfield et al, 1974;Quinn et al, 1975;Peng et al, 1975: Martin et al, 1975Broughton et al, 1975;Gibbons et al, 1976Goodford et al, 1976;Rouot et al, 1976;Martin, 1978bl. Those of us working in the field have no doubt that better and better examples of the predictive value of QSAR will be published.…”

Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5‐Triazin‐2‐one Ring Opening

“…Amidinoureas (or amidoguanidines) are a group of compounds presenting a specific 7-heavy atoms function consisting of the N-substitution of a urea function with an amidine. This structure presents tautomery ability and can be diversely substituted at N 1 , N 2 , and N 3 (Figure 1). This chemical function naturally occurs in bioactive molecules, but it also plays a role as important pharmacophore in medicinal chemistry.…”

“…This chemical function naturally occurs in bioactive molecules, but it also plays a role as important pharmacophore in medicinal chemistry. [1] Both natural products and synthetic molecules bearing an amidinourea proved to show useful pharmacological and biological properties such as antimalarial, [2] antibacterial, [3] antifungal, [4] antiviral, [5] and anticancer. [6] Representative examples include i. N 1 -substituted biclodil (1) -an effective drug for the treatment of coccidiosis, which also showed vasodilator effects in acute heart failure; [7] ii.…”