Synthesis and histamine H3 receptor activity of 4-(n-alkyl)-1H-imidazoles and 4-(omega-phenylalkyl)-1H-imidazoles.
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.
De Esch
I J
IJ
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Gaffar
A
A
Menge
W M
WM
Timmerman
H
H
D000818:Animals; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D006633:Histamine Antagonists; D007093:Imidazoles; D018100:Receptors, Histamine H3