RESUMO
Reaction of 3-amino derivatives of the nematocides tetramisole and levamisole with variously substituted benzoylisocyanates gave a series of benzoylureas I which were tested for activity against helminths and ectoparasites. Compounds bearing 2,6-difluoro and 4-trifluoromethyl substituents had potent nematocidal activity in both mice and sheep. No antiectoparasitic activity was observed.
Assuntos
Anti-Helmínticos/síntese química , Animais , Anti-Helmínticos/uso terapêutico , Fenômenos Químicos , Química , Feminino , Levamisol/análogos & derivados , Masculino , Camundongos , Infecções por Nematoides/tratamento farmacológico , Ovinos , Relação Estrutura-Atividade , Tetramizol/análogos & derivadosRESUMO
Structure-activity relationships in the region of the phthalide ring of the inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been explored. Replacement of the lactone ring with other cyclic moieties resulted in loss of potency, especially for larger groups. Replacement of the ring by acyclic substituents also indicated a strong sensitivity to steric bulk. A phenolic hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be essential for high potency. The aromatic methyl group was essential for activity; the methoxyl group could be replaced by ethyl to give a compound with 2-4 times the potency of mycophenolic acid in vitro and in vivo.