Selective antagonists of mouse trace amine-associated receptor 1 (mTAAR1): discovery of EPPTB (RO5212773)

Henri Stalder; Marius C Hoener; Roger D Norcross

doi:10.1016/j.bmcl.2010.12.075

Selective antagonists of mouse trace amine-associated receptor 1 (mTAAR1): discovery of EPPTB (RO5212773)

Bioorg Med Chem Lett. 2011 Feb 15;21(4):1227-31. doi: 10.1016/j.bmcl.2010.12.075. Epub 2010 Dec 21.

Authors

Henri Stalder¹, Marius C Hoener, Roger D Norcross

Affiliation

¹ F. Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland. henri.stalder@roche.com

PMID: 21237643
DOI: 10.1016/j.bmcl.2010.12.075

Abstract

High throughput screening of the Roche compound library identified benzanilides such as 1 and 2 as antagonists of TAAR1. Optimisation of this hit series led to the first selective TAAR1 antagonist (N-(3-Ethoxy-phenyl)-4-pyrrolidin-1-yl-3-trifluoromethyl-benzamide EPPTB (RO5212773, 9f) having IC(50) of 28 nM at mouse TAAR1.

MeSH terms

Animals
Benzamides / chemical synthesis
Benzamides / chemistry*
Benzamides / pharmacology
Drug Evaluation, Preclinical
High-Throughput Screening Assays
Humans
Mice
Microsomes, Liver / metabolism
Protein Binding
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry*
Pyrrolidines / pharmacology
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, G-Protein-Coupled / metabolism
Structure-Activity Relationship

Substances

Benzamides
N-(3-ethoxyphenyl)-4-pyrrolidin-1-yl-3-trifluoromethylbenzamide
Pyrrolidines
Receptors, G-Protein-Coupled
Trace amine-associated receptor 1