Synthesis of 2-(5-Bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues and their binding affinities for dopamine D2, D3, and D4 receptors

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

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A series of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues was prepared and their affinity for dopamine D2, D3, and D4 receptors was measured using in vitro binding assays. The results of receptor binding studies indicated that the incorporation of a pyrrole moiety between the phenyl ring and the basic nitrogen resulted in a significant increase in the selectivity for dopamine D3 receptors. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-5-(2-(3-pyridal)piperidinyl)methyl-1H-pyrrole (6p), which has a D3 receptor affinity of 4.3 nM, a 20-fold selectivity for D3 versus D2 receptors, and a 300-fold selectivity for D3 versus D4 receptors. This compound is predicted to be a useful ligand for studying the functional role of dopamine D3 receptors in vivo.

Original languageEnglish
Pages (from-to)225-233
Number of pages9
JournalBioorganic and Medicinal Chemistry
Issue number2
Publication statusPublished - 17 Jan 2003


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