De Esch I J, Gaffar A, Menge W M, Timmerman H
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Bioorg Med Chem. 1999 Dec;7(12):3003-9. doi: 10.1016/s0968-0896(99)00253-9.
The influence of lipophilic moieties attached to a 4-1H-imidazole ring on the histamine H3 receptor activity was systematically investigated. Series of 4-(n-alkyl)-1H-imidazoles and 4-(omega-phenylalkyl)-1H-imidazoles were prepared, with an alkyl chain varying from 2-9 methylene groups and from 1-9 methylene groups, respectively. The compounds were tested for their activity on the H3 receptor under in vitro conditions. For the 4-(n-alkyl)-1H-imidazoles the activity is proportional to chain length, ranging from a pA2 value of 6.3 +/- 0.2 for 4-(n-propyl)-1H-imidazole to a pA2 value of 7.2 +/- 0.1 for 4-(n-decyl)-1H-imidazole. For the series 4-(omega-phenylalkyl)-4H-imidazoles an optimum in H3 activity was found for the pentylene spacer: 4-(omega-phenylpentyl)-1H-imidazole has a pA2 value of 7.8 +/- 0.1.
系统研究了连接在4-1H-咪唑环上的亲脂性部分对组胺H3受体活性的影响。制备了一系列4-(正烷基)-1H-咪唑和4-(ω-苯烷基)-1H-咪唑，烷基链分别含有2至9个亚甲基和1至9个亚甲基。在体外条件下测试了这些化合物对H3受体的活性。对于4-(正烷基)-1H-咪唑，活性与链长成比例，4-(正丙基)-1H-咪唑的pA2值为6.3±0.2，4-(正癸基)-1H-咪唑的pA2值为7.2±0.1。对于4-(ω-苯烷基)-4H-咪唑系列，发现戊烯间隔基的H3活性最佳：4-(ω-苯戊基)-1H-咪唑的pA2值为7.8±0.1。
