RESUMEN
Anthelmintic efficacies of a series of 6-substituted methyl imidazo[1,2-alpha]pyridine-2-carbamates were compared to similarly substituted benzimidazole-2-carbamates. With only one exception, methyl 6-benzoylimidazo[1,2-alpha]pyridine-2-carbamate, both classes of compounds exhibited similar activity vs. Nematospiroides dubius in mice. Preliminary screening indicated methyl 6-(1,2,2-trichloroethenyl)imidazo[1,2-alpha]pyridine-2-carbamate to be the most potent derivative in the series. However, evaluation in sheep indicated that its anthelmintic spectrum was inferior to methyl 6-(phenylsulfinyl)imidazo[1,2-alpha]pyridine-2-carbamate.
Asunto(s)
Antihelmínticos/síntesis química , Bencimidazoles/síntesis química , Imidazoles/síntesis química , Animales , Bencimidazoles/farmacología , Carbamatos/síntesis química , Carbamatos/farmacología , Fenómenos Químicos , Química , Imidazoles/farmacología , Ratones , Infecciones por Nematodos/tratamiento farmacológico , Piridinas/síntesis química , Piridinas/farmacología , Ovinos , Relación Estructura-ActividadRESUMEN
A series of methyl imidazo-[11,2-a]pyridine-2-carbamates was synthesized for anthelmintic testing. The preparation of this class of compounds was simplified by utilization of a novel one-step condensation of the appropriately substituted 2-aminopyridine and methyl chloroacetylcarbamate. The most potent compound, methyl 6-(phenylsulfinyl)-imidazo[1,2-a]pyridine-2-carbamate, was orally effective against a broad range of helminths in sheep and cattle, at a dosage of 2.5 mg/kg. Limited trials in swine and dogs demonstrated anthelmintic activity at higher dosages. Limited observations in sheep and cattle indicated that, in both species, a single oral dose of 200 mg/kg was well tolerated.
Asunto(s)
Antihelmínticos/síntesis química , Carbamatos/síntesis química , Piridinas/síntesis química , Animales , Antihelmínticos/uso terapéutico , Carbamatos/farmacología , Carbamatos/uso terapéutico , Bovinos , Perros , Ratones , Infecciones por Nematodos/tratamiento farmacológico , Piridinas/farmacología , Piridinas/uso terapéutico , Ovinos , PorcinosRESUMEN
The synthesis and fasciolicidal activity of 4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide are reported. A single dose of 15 mg/kg was effective in removing over 90% of immature Fasciola hepatica from sheep (6 weeks after infection) and calves (8 weeks after infection). A 2.5 mg/kg dose removed over 90% of mature (16 weeks old) liver fluke from sheep. Single oral doses up to 400 mg/kg were tolerated by sheep without gross toxic symptoms.
Asunto(s)
Antihelmínticos/uso terapéutico , Fascioliasis/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Animales , Antihelmínticos/síntesis química , Antihelmínticos/toxicidad , Bovinos , Fasciola hepatica , Ovinos , Sulfanilamidas , Sulfonamidas/síntesis química , Sulfonamidas/toxicidad , Tricloroetileno/análogos & derivados , Tricloroetileno/síntesis química , Tricloroetileno/uso terapéuticoRESUMEN
The antiprotozoal drug 3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole (I), which exhibits activity against trypanosomiasis, is also antibacterial in vivo. Since the urine from a dog dosed with I showed a broader spectrum of antibacterial activity than I itself, metabolites from this urine were isolated and partially characterized. The metabolites were mono- and dihydroxy-substituted species with the hydroxyl groups on carbons 4--7 of the hexahydrobenzisoxazole ring. These observations led to the synthesis of several such hydroxy derivatives of I, and their properties fully supported the proposed positions of metabolic hydroxylation. One synthetic compound, the 6,7-cis-dihydroxy compound, exhibited higher antibacterial activity against Salmonella schottmuelleri in mice and greater trypanocidal activity in vivo against Trypanosoma cruzi (Brazil strain) than I.