Design, Synthesis, and Evaluation of Thyronamine Analogues as Novel Potent Mouse Trace Amine Associated Receptor 1 (mTAAR1) Agonists

Trace amine associated receptor 1 (TAAR1) is a G protein coupled receptor (GPCR) expressed in brain and periphery activated by a wide spectrum of agonists that include, but are not limited to, trace amines (TAs), amphetamine-like psychostimulants, and endogenous thyronamines such as thyronamine (T0A...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of medicinal chemistry Vol. 58; no. 12; pp. 5096 - 5107
Main Authors:	Chiellini, Grazia, Nesi, Giulia, Digiacomo, Maria, Malvasi, Rossella, Espinoza, Stefano, Sabatini, Martina, Frascarelli, Sabina, Laurino, Annunziatina, Cichero, Elena, Macchia, Marco, Gainetdinov, Raul R, Fossa, Paola, Raimondi, Laura, Zucchi, Riccardo, Rapposelli, Simona
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 25-06-2015
Subjects:	Amino Acid Sequence Animals Blood Glucose - metabolism Drug Design HEK293 Cells Humans Ligands Male Mice Models, Molecular Molecular Sequence Data Rats, Wistar Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - chemistry Receptors, G-Protein-Coupled - metabolism Small Molecule Libraries - chemistry Small Molecule Libraries - pharmacology Thyronines - chemistry Thyronines - pharmacology
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Trace amine associated receptor 1 (TAAR1) is a G protein coupled receptor (GPCR) expressed in brain and periphery activated by a wide spectrum of agonists that include, but are not limited to, trace amines (TAs), amphetamine-like psychostimulants, and endogenous thyronamines such as thyronamine (T0AM) and 3-iodothyronamine (T1AM). Such polypharmacology has made it challenging to understand the role and the biology of TAAR1. In an effort to understand the molecular basis of TAAR1 activation, we rationally designed and synthesized a small family of thyronamine derivatives. Among them, compounds 2 and 3 appeared to be a good mimic of the parent endogenous thyronamine, T0AM and T1AM, respectively, both in vitro and in vivo. Thus, these compounds offer suitable tools for studying the physiological roles of mouse TAAR1 and could represent the starting point for the development of more potent and selective TAAR1 ligands.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-2623 1520-4804
DOI:	10.1021/acs.jmedchem.5b00526