Synthesis and histamine H3 receptor activity of 4-(n-alkyl)-1H-imidazoles and 4-(omega-phenylalkyl)-1H-imidazoles

I J De Esch, A. Gaffar, W M Menge, H Timmerman

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)3003-9
Number of pages7
JournalBioorganic and Medicinal Chemistry
Issue number12
Publication statusPublished - Dec 1999


  • Animals
  • Guinea Pigs
  • Histamine Antagonists
  • Imidazoles
  • In Vitro Techniques
  • Jejunum
  • Magnetic Resonance Spectroscopy
  • Receptors, Histamine H3
  • Structure-Activity Relationship
  • Journal Article
  • Research Support, Non-U.S. Gov't


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