RESUMO
A series of compounds possessing both H(1) histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observed in vivo, as was increased CYP3A4 inhibition compared to their respective single-function drugs. Selected analogs in the series were shown to be orally active in guinea pig models.
Assuntos
Cetirizina/química , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Inibidores de Lipoxigenase , Loratadina/química , Animais , Cetirizina/farmacocinética , Cobaias , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/química , Loratadina/farmacocinética , Modelos Animais , Estrutura Molecular , Ratos , Relação Estrutura-AtividadeRESUMO
Treatment of dextromethorphan 1 with various alkylating agents followed by base treatment led to Hoffman-type elimination reactions to produce a series of tricyclic derivatives, 6. These derivatives were characterized in vitro as sigma-1 receptor ligands.
