Janssens F, Torremans J, Janssen M, Stokbroekx R A, Luyckx M, Janssen P A
J Med Chem. 1985 Dec;28(12):1934-43. doi: 10.1021/jm00150a029.
The synthesis of a series of 1-[(4-fluorophenyl)methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-ami nes and the preliminary evaluation of their in vivo antihistamine activity are described. The title compounds were obtained starting from either 1, 4, 10, or 55 by different synthetic methods. Substitution on the phenyl nucleus of the benzimidazole ring (84-87) was achieved by two different approaches. The in vivo antihistamine activity was evaluated by the compound 48/80 induced lethality test in rats and the antihistamine-induced lethality test in guinea pigs after oral and/or subcutaneous administration. The duration of action was studied in the guinea pig for three compounds (4, 51, and 55). Compound 51, "astemizole", was also studied in histamine- and serotonin-induced cutaneous reaction and for mydriatic activity in the rat and tested for peripheral and central effects not related to histamine antagonism in a variety of systems. Astemizole has been selected for clinical investigation.
描述了一系列1-[(4-氟苯基)甲基]-N-(4-哌啶基)-1H-苯并咪唑-2-胺的合成及其体内抗组胺活性的初步评价。通过不同的合成方法，从1、4、10或55开始获得标题化合物。苯并咪唑环的苯基核上的取代（84 - 87）通过两种不同的方法实现。通过在大鼠中进行化合物48/80诱导的致死率试验以及在豚鼠中口服和/或皮下给药后进行抗组胺诱导的致死率试验来评价体内抗组胺活性。在豚鼠中研究了三种化合物（4、51和55）的作用持续时间。化合物51，即“阿司咪唑”，还在组胺和血清素诱导的皮肤反应中进行了研究，并在大鼠中进行了散瞳活性研究，并在各种系统中测试了与组胺拮抗作用无关的外周和中枢作用。阿司咪唑已被选用于临床研究。
