Details

Autor(en) / Beteiligte

• Micheli, Fabrizio
• Bonanomi, Giorgio
• Blaney, Frank E
• Braggio, Simone
• Capelli, Anna Maria
• Checchia, Anna
• Curcuruto, Ornella
• Damiani, Federica
• Di Fabio, Romano
• Donati, Daniele
• Gentile, Gabriella
• Gribble, Andy
• Hamprecht, Dieter
• Tedesco, Giovanna
• Terreni, Silvia
• Tarsi, Luca
• Lightfoot, Andrew
• Stemp, Geoff
• MacDonald, Gregor
• Smith, Alex
• Pecoraro, Michela
• Petrone, Marcella
• Perini, Ornella
• Piner, Jacqui
• Rossi, Tino
• Worby, Angela
• Pilla, Maria
• Valerio, Enzo
• Griffante, Cristiana
• Mugnaini, Manolo
• Wood, Martyn
• Scott, Claire
• Andreoli, Michela
• Lacroix, Laurent
• Schwarz, Adam
• Gozzi, Alessandro
• Bifone, Angelo
• Ashby, Charles R
• Hagan, Jim J
• Heidbreder, Christian

Titel

1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines:  A Series of Potent and Selective Dopamine D3 Receptor Antagonists

Ist Teil von

• Journal of medicinal chemistry, 2007-10, Vol.50 (21), p.5076-5089

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2007

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The discovery of new highly potent and selective dopamine D3 receptor antagonists has recently permitted characterization of the role of the dopamine D3 receptor in a wide range of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine-seeking behavior in the rat, reduces oral operant alcohol self-administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.