ABSTRACT
A series of isomeric imidazo[1,2-alpha]pyridine-2-carbamates was prepared for testing as anthelmintics. The analogues were synthesized by reacting the appropriate 2-aminopyridine and methyl chloroacetylcarbamate. Steric hindrance in the 2,6-disubstituted derivative resulted in the formation of the isomeric 3-substituted analogue as the major product. Carbon-13 NMR proved useful in the structural assignments in this series. None of the analogues exhibited the potency of methyl 6-(phenylsulfinyl)imidazo[1,2-alpha]pyridine-2-carbamate when tested against Nematospiroides dubius in mice.
Subject(s)
Anthelmintics/chemical synthesis , Imidazoles/chemical synthesis , Animals , Carbamates/chemical synthesis , Carbamates/pharmacology , Chemical Phenomena , Chemistry , Imidazoles/pharmacology , Isomerism , Mice , Nematode Infections/drug therapyABSTRACT
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.
Subject(s)
Anthelmintics/chemical synthesis , Benzimidazoles/chemical synthesis , Imidazoles/chemical synthesis , Animals , Benzimidazoles/pharmacology , Carbamates/chemical synthesis , Carbamates/pharmacology , Chemical Phenomena , Chemistry , Imidazoles/pharmacology , Mice , Nematode Infections/drug therapy , Pyridines/chemical synthesis , Pyridines/pharmacology , Sheep , Structure-Activity RelationshipABSTRACT
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.
Subject(s)
Anthelmintics/chemical synthesis , Carbamates/chemical synthesis , Pyridines/chemical synthesis , Animals , Anthelmintics/therapeutic use , Carbamates/pharmacology , Carbamates/therapeutic use , Cattle , Dogs , Mice , Nematode Infections/drug therapy , Pyridines/pharmacology , Pyridines/therapeutic use , Sheep , SwineABSTRACT
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.
