Further studies of the relationship of anthelmintic activity to structure of quaternary piperazines

Abstract The in vivo activity against the mouse pinworm Syphacia obvelata and, in some cases, the acute oral LD 50 in the mouse, are reported for a group of piperazines quaternized on one or both ring nitrogens. The effect on this anthelmintic activity of variations in the substituents on the nitrogens and of changes in the number and position of methyl groups on the ring carbons have been studied. The maximum of therapeutic index is found to occur in two series of bis-quaternary salts when each nitrogen is substituted by a methyl group and a decyl, undecyl, or dodecyl group. The effect of differing solubilities of different salts of the same cation on anthelmintic activity and on toxicity is shown. Variation of the therapeutic index with the steric configuration of the cation has been found in two cases where more than one stereoisomeric quaternary halide has been isolated. The best compound reported here is the highest-melting isomer of 1,4-( 2,5-trans- )-tetramethyl-1,4,-bis-dodecylpiperazinium chloride (Table 1, line 30).