Exploring the structure-activity relationship of the ethylamine portion of 3-iodothyronamine for rat and mouse trace amine-associated receptor 1

Edwin S. Tan, Motonori Miyakawa, James R. Bunzow, David K. Grandy, Thomas S. Scanlan

    Research output: Contribution to journalArticlepeer-review

    47 Scopus citations

    Abstract

    3-Iodothyronamine (1, T1AM) is a naturally occurring derivative of thyroid hormone that can potently activate the orphan G protein-coupled receptor (GPCR) known as the trace amine-associated receptor 1 (TAAR 1). We have previously found that modifying the outer ring of the phenoxyphenethylamine core scaffold of 1 can improve potency and provide potent agonists. In this study, we explored the tolerance of rat and mouse TAAR 1 (rTAAR1 and mTAAR1) for structural modifications in the ethylamine portion of 1. We found that incorporating unsaturated hydrocarbon substituents and polar, hydrogen-bond-accepting groups were beneficial for rTAAR1 and mTAAR1, respectively, providing compounds that were equipotent or more potent than 1. Additionally, we have discovered that a naphthyl group is an excellent isosteric replacement for the iodophenyl ring of 1.

    Original languageEnglish (US)
    Pages (from-to)2787-2798
    Number of pages12
    JournalJournal of Medicinal Chemistry
    Volume50
    Issue number12
    DOIs
    StatePublished - Jun 14 2007

    ASJC Scopus subject areas

    • Molecular Medicine
    • Drug Discovery

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