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 journalArticle

40 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

Fingerprint Dive into the research topics of 'Exploring the structure-activity relationship of the ethylamine portion of 3-iodothyronamine for rat and mouse trace amine-associated receptor 1'. Together they form a unique fingerprint.

  • Cite this