Janssens F, Torremans J, Janssen M, Stokbroekx R A, Luyckx M, Janssen P A
J Med Chem. 1985 Dec;28(12):1925-33. doi: 10.1021/jm00150a028.
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.
描述了一系列N-(4-哌啶基)-1H-苯并咪唑-2-胺的合成及其体外和体内抗组胺活性的初步评价。(2-氨基苯基)硫脲与氧化汞(II)进行环脱硫反应生成2-氨基苯并咪唑中间体，该中间体在内氮原子上进行单烷基化反应。用48%氢溴酸水溶液脱除哌啶氮原子上的保护基后，通过三种不同方法，即烷基化、还原胺化或环氧乙烷开环反应得到标题化合物。在大鼠中通过化合物48/80诱导致死试验以及在豚鼠中通过组胺诱导致死试验，在口服和/或皮下给药后评价体内抗组胺活性。对选定数量的化合物，在豚鼠中研究了其作用持续时间。苯乙基衍生物在两种动物口服给药后均表现出最有效的抗组胺特性。
