Abstract
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 language | English |
|---|---|
| Pages (from-to) | 3003-9 |
| Number of pages | 7 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 7 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1999 |
Keywords
- 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