1,2,4-Triazolyl azabicyclo[3.1.0]hexanes: a new series of potent and selective dopamine D(3) receptor antagonists
| Autor: | Frank E. Blaney, Christian Heidbreder, Anna Checchia, Manolo Mugnaini, Charles R. Ashby, Romano Di-Fabio, Luca Arista, Dieter Hamprecht, Cristiana Griffante, Fabrizio Micheli, Stefano Fontana, Emiliangelo Ratti, Federica Damiani, Anna Maria Capelli, Luca Tarsi, Angela Worby, Carla Marchioro, Giovanna Tedesco, Silvia Terreni, Giorgio Bonanomi, Jacqui Piner, Gabriella Gentile, Simone Braggio |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Guinea Pigs Pharmacology Nicotine Structure-Activity Relationship In vivo Dopamine receptor D3 Dopamine Drug Discovery medicine Potency Animals Hexanes Humans Computer Simulation Receptor Molecular Structure Chemistry Cell Membrane Receptors Dopamine D3 Stereoisomerism Conditioned place preference Biochemistry Models Chemical Drug Design Models Animal Molecular Medicine Antagonism medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 53(1) |
| ISSN: | 1520-4804 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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