NOVEL ANTHELMINTIC AGENTS .2. PYRANTEL AND OTHER CYCLIC AMIDINES

Broad-spectrum anthelmintic activity lias been discovered in a novel series of imidazolines and tetrahydropyrimidines substituted variously at the 2 positions by 2-arylethyl or 2-arylyinyl groups. One member of this series, trans-1,4,5,6-tetrahydro-1-methyl-2-(2-(2-thieiiyl)vinvl|pyrimidine tartrate (pyrantel tartrate, 71) has gained acceptance as a veterinary anthelmintic agent in many areas of the world. The decreasing order of potency for the various aryl systems is 2-thienyl > 3-thienyl > phenyl > 2-furyl. The arylyinyl analog is usually more potent than the corresponding arylethyl compound. N-Methyl substitution on the cyclic amidine system invariably results in increased potency: substitution at almost any other position results in the loss of potency or of activity altogether. One notable exception is that certain substituents can be placed at the ortho position of the aryl system without detriment to anthelmintic activity, and in some cases enhanced potency is achieved. Thus, besides pyrantel, some of the more potent compounds in this series are tans-1,4,5,6-tetrahydro-1-methyl-2-[2-(3-methy1-2-thienyl)vinyl]pyrimidine (74), trans-1,4,5,6-tetrahydro-1-methyl-2-(2-melhylstyryl)pyrimidine(84), trans-2-(2-bromostyryl)-1,4,5,6-tetrahydro-1-methylpyrimidine (97), and trans-2-(2-chlorostyryl)-1,4,5,6-tetrahydro-1-methylpyrimidine (93). © 1969, American Chemical Society. All rights reserved.