Synthesis of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole analogues and their binding affinities for dopamine D2 and D3 receptors

Yunsheng Huang, Robert R. Luedtke, Rebekah A. Freeman, Li Wu, Robert H. Mach

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

A series of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole derivatives was prepared and their affinity for dopamine D2 and D3 receptors was measured using in vitro binding assays. Several oxadiazole analogues were also prepared and tested for their affinity for dopamine D2 and D3 receptors. The results of receptor binding studies indicated that the incorporation of an imidazole moiety between the phenyl ring and the basic nitrogen did not significantly increase the selectivity for dopamine D3 receptors, whereas the incorporation of an oxadiazole at the same region resulted in a total loss of affinity for both dopamine receptor subtype binding sites. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-4-(6,7-dimethoxy-1,2,3, 4-tetrahydroisoquinolinomethyl)imidazole (5i), which has a D3 receptor affinity of 21 nM and a 7-fold selectivity for D3 versus D2 receptors. The binding affinity for σ1 and σ2 receptors was also measured, and the results showed that several analogues were selective σ1 receptor ligands.

Original languageEnglish
Pages (from-to)3113-3122
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume9
Issue number12
DOIs
StatePublished - 27 Nov 2001

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