2. Academic Validation
  3. 1,2,4-Triazolyl azabicyclo[3.1.0]hexanes: a new series of potent and selective dopamine D(3) receptor antagonists

1,2,4-Triazolyl azabicyclo[3.1.0]hexanes: a new series of potent and selective dopamine D(3) receptor antagonists

  • J Med Chem. 2010 Jan 14;53(1):374-91. doi: 10.1021/jm901319p.
Fabrizio Micheli 1,  Luca Arista,  Giorgio Bonanomi,  Frank E Blaney,  Simone Braggio,  Anna Maria Capelli,  Anna Checchia,  Federica Damiani,  Romano Di-Fabio,  Stefano Fontana,  Gabriella Gentile,  Cristiana Griffante,  Dieter Hamprecht,  Carla Marchioro,  Manolo Mugnaini,  Jacqui Piner,  Emiliangelo Ratti,  Giovanna Tedesco,  Luca Tarsi,  Silvia Terreni,  Angela Worby,  Charles R Ashby Jr,  Christian Heidbreder
Affiliations

Affiliation

  • 1 Neurosciences Centre of Excellence, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. Fabrizio.E.Micheli@gsk.com
PMID: 19891474 DOI: 10.1021/jm901319p
Abstract

The discovery of new highly potent and selective dopamine (DA) D(3) receptor antagonists has recently allowed the characterization of the DA D(3) receptor in a range of preclinical animal models of drug addiction. A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes, members of which showed a high affinity and selectivity for the DA D(3) receptor and excellent pharmacokinetic profiles, is reported here. Members of a group of derivatives from this series showed good oral bioavailability and brain penetration and very high in vitro affinity and selectivity for the DA D(3) receptor, as well as high in vitro potency for antagonism at this receptor. Several members of this series also significantly attenuate the expression of conditioned place preference (CPP) to nicotine and cocaine.

Figures
Products