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) of 28 nM at mouse TAAR1.
F. Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland. henri.stalder@roche.com
Henri
H
Stalder
Marius C
MC
Hoener
Roger D
RD
Norcross
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000095383:Trace Amine-Associated Receptors
D001549:Benzamides; D011759:Pyrrolidines; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors; C546333:N-(3-ethoxyphenyl)-4-pyrrolidin-1-yl-3-trifluoromethylbenzamide