The efficacy of a novel compound, (e)-1-(4'-bromo-4-biphenylyl)-1-(4-chlorophenyl)-3-dimethylaminoprop-1-ene against Trypanosoma cruzi in mice.

The biological properties of a novel compound 353C with high activity against Trypanosoma cruzi, are described. The compound was about 10 times and 20 times more effective than either benznidazole or nifurtimox respectively, in producing radical cure in mice. 353C has a long half-life and showed anti-trypanosomal properties when given to mice at weekly intervals.

The activity against Trypanosoma cruzi and cutaneous leishmaniasis, and toxicity, of moxipraquine (349C59).

A novel 8-aminoquinolone compound, 8(6-4' 3-hydroxybutyl)piperazin-1'-ylhexylamino)-6-methoxyquinoline di(hydrogen maleate), moxipraquine, 349C59, was shown to be active against experimental infections with Trypanosoma cruzi. It was effective in suppressing parasitaemia but did not eradicate the infection from mice or guinea-pigs. Other clinically tested drugs, including nifurtimox, were likewise incapable of eradicating the parasite from infected mice. Moxipraquine was less potent against mouse infections with strain Peru than it was against other strains of T. cruzi. In limited tests, moxipraquine was effective on experimental infections of Leishmania major, L. mexicana mexicana and L. brasiliensis panamensis but not L.b. brasiliensis. Significant foetal toxicity, observed experimentally in rats and rabbits, resulted in the termination of clinical trials.

Mathematical prediction of drug distribution in vivo: studies with doxantrazole in rats.

A pharmacokinetic model incorporating 14 compartments and 29 transfer coefficients has been developed from experimental data obtained after intravenous administration of a single dose to describe the distribution of doxantrazole in the rate. The distribution calculated from the model agreed closely with that determined experimentally. In addition, the model was able to predict with considerable accuracy the distribution of doxantrazole after repeated dosing.