New antihistaminic N-heterocyclic 4-piperidinamines. 1. Synthesis and antihistaminic activity of N-(4-piperidinyl)-1H-benzimidazol-2-amines.
The synthesis of a series N-(4-piperidinyl)-1H-benzimidazol-2-amines and the preliminary evaluation of their in vitro and in vivo antihistaminic activity are described. Cyclodesulfurization of (2-aminophenyl)thioureas with mercury(II) oxide resulted in 2-aminobenzimidazole intermediates, which were monoalkylated on the endo-nitrogen atom. After deprotection of the piperidine nitrogen atom with 48% aqueous hydrobromic acid solution, the title compounds were obtained by three different methods, viz. alkylation, reductive amination, or oxirane ring-opening reactions. The in vivo antihistaminic activity was evaluated by the compound 48/80 induced lethality test in rats and histamine-induced lethality test in guinea pigs after oral and/or subcutaneous administration. The duration of action, for a selected number of compounds, was studied in the guinea pig. The phenylethyl derivatives showed the most potent antihistamine properties after oral administration in both animal species.
D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001681:Biological Assay; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D007082:Ileum / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D001562:Benzimidazoles; D006633:Histamine Antagonists; D010880:Piperidines; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine