title: Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists.
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.
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Guido
authors.initials: G
authors.lastname: Galley
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Angélica
authors.initials: A
authors.lastname: Beurier
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Décoret
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Annick
authors.initials: A
authors.lastname: Goergler
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Roman
authors.initials: R
authors.lastname: Hutter
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mohr
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Axel
authors.initials: A
authors.lastname: Pähler
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schmid
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Türck
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Unger
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Katrin Groebke
authors.initials: KG
authors.lastname: Zbinden
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Marius C
authors.initials: MC
authors.lastname: Hoener
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , CH-4070 Basel, Switzerland.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Norcross
keywords: 2-aminooxazoline; SAR; TAAR1 agonist; schizophrenia