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

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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2011-02, Vol.21 (4), p.1227-1231
Main Authors: Stalder, Henri, Hoener, Marius C., Norcross, Roger D.
Format: Article
Language:English
Subjects:
Animals
Antagonists
Benzamides - chemical synthesis
Benzamides - chemistry
Benzamides - pharmacology
Benzanilides
Biological and medical sciences
chemistry
Drug Evaluation, Preclinical
EPPTB
High-Throughput Screening Assays
Humans
inhibitory concentration 50
Inverse agonists
Medical sciences
Mice
Microsomes, Liver - metabolism
Miscellaneous
Pharmacology. Drug treatments
Protein Binding
Pyrrolidines - chemical synthesis
Pyrrolidines - chemistry
Pyrrolidines - pharmacology
Receptors, G-Protein-Coupled - antagonists & inhibitors
Receptors, G-Protein-Coupled - metabolism
RO5212773
screening
Structure-Activity Relationship
TAAR1
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.12.075