Synthesis and histamine H3 receptor activity of 4-(n-alkyl)-1H-imidazoles and 4-(ω-phenylalkyl)-1H-imidazoles Original Research Article

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-(ω-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-(ω-phenylalkyl)-4H-imidazoles an optimum in H3 activity was found for the pentylene spacer: 4-(ω-phenylpentyl)-1H-imidazole has a pA2 value of 7.8±0.1.