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New antihistaminic N-heterocyclic 4-piperidinamines. 1. Synthesis and antihistaminic activity of N-(4-piperidinyl)-1H-benzimidazol-2-amines.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Janssens F,Torremans J,Janssen M,Stokbroekx RA,Luyckx M,Janssen PA

doi

10.1021/jm00150a028

subject

Has Abstract

pub_date

1985-12-01 00:00:00

pages

1925-33

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

28

pub_type

杂志文章

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