Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists

  • ACS Med Chem Lett. 2015 Dec 30;7(2):192-7. doi: 10.1021/acsmedchemlett.5b00449.
Guido Galley  1 ,  Angélica Beurier  1 ,  Guillaume Décoret  1 ,  Annick Goergler  1 ,  Roman Hutter  1 ,  Susanne Mohr  1 ,  Axel Pähler  1 ,  Philipp Schmid  1 ,  Dietrich Türck  1 ,  Robert Unger  1 ,  Katrin Groebke Zbinden  1 ,  Marius C Hoener  1 ,  Roger D Norcross  1
Affiliations
  • 1. Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
PMID: 26985297 DOI: 10.1021/acsmedchemlett.5b00449
Abstract

2-Aminooxazolines were discovered as a novel structural class of TAAR1 ligands. Starting from a known adrenergic compound 1, structural modifications were made to obtain highly potent and selective TAAR1 ligands such as 12 (RO5166017), 18 (RO5256390), 36 (RO5203648), and 48 (RO5263397). These compounds exhibit drug-like physicochemical properties, have good oral bioavailability, and display in vivo activity in a variety of animal models relevant for psychiatric diseases and addiction.

Keywords
2-aminooxazoline; SAR; TAAR1 agonist; schizophrenia.
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