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.

Synthesis and Anti‐Plasmodium Activity of Benzimidazole Analogues Structurally Related to Astemizole

“…[19] Lately, the palladium-catalyzed amination of 2-chlorobenzimidazoles, based on Buchwald chemistry, has also been described. [20,21] Despite recent advances towards a more direct synthesis of 2-aminobenzimidazoles, the synthetic approach in Janssen's seminal article [22] was preferred for our work because it does not use expensive catalysts, microwave irradiation, or high temperatures leading to undesired byproducts.…”

Design and synthesis of substituted imidazole and triazole N-phenylbenzo[d]oxazolamine inhibitors of retinoic acid metabolizing enzyme CYP26

“…The product was obtained in high yield and was pure enough for use in the next step. Cyclisation of the isocyanate 3 to form the benzoxazole 4 was achieved by reaction with 2-aminophenol in the presence of mercury oxide and catalytic sulphur [22]. Introduction of the imidazole to give the required product 5 involved reaction with carbonyldiimidazole (CDI) and imidazole [23] with subsequent purification by column chromatography.…”

A high yielding oxidation method for the preparation of substituted 2,3-dihydro-4-pyridones from 4-piperidones

“…The organic layer was washed twice with water, once with brine, dried over MgSO 4 and concentrated under reduced pressure. The crude residue was purified by flash silica chromatography to give 1.94 g (90%) of the intermediate acetal 19 …”