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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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2011-02, Vol.21 (4), p.1227-1231
Hauptverfasser:	Stalder, Henri, Hoener, Marius C., Norcross, Roger D.
Format:	Artikel
Sprache:	eng
Schlagworte:	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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Zusammenfassung:	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