title: 1,2,4-Triazolyl azabicyclo[3.1.0]hexanes: a new series of potent and selective dopamine D(3) receptor antagonists.
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.
authors.affiliation: Neurosciences Centre of Excellence, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. Fabrizio.E.Micheli@gsk.com
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Micheli
authors.forename: Luca
authors.initials: L
authors.lastname: Arista
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bonanomi
authors.forename: Frank E
authors.initials: FE
authors.lastname: Blaney
authors.forename: Simone
authors.initials: S
authors.lastname: Braggio
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Capelli
authors.forename: Anna
authors.initials: A
authors.lastname: Checchia
authors.forename: Federica
authors.initials: F
authors.lastname: Damiani
authors.forename: Romano
authors.initials: R
authors.lastname: Di-Fabio
authors.forename: Stefano
authors.initials: S
authors.lastname: Fontana
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gentile
authors.forename: Cristiana
authors.initials: C
authors.lastname: Griffante
authors.forename: Dieter
authors.initials: D
authors.lastname: Hamprecht
authors.forename: Carla
authors.initials: C
authors.lastname: Marchioro
authors.forename: Manolo
authors.initials: M
authors.lastname: Mugnaini
authors.forename: Jacqui
authors.initials: J
authors.lastname: Piner
authors.forename: Emiliangelo
authors.initials: E
authors.lastname: Ratti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tedesco
authors.forename: Luca
authors.initials: L
authors.lastname: Tarsi
authors.forename: Silvia
authors.initials: S
authors.lastname: Terreni
authors.forename: Angela
authors.initials: A
authors.lastname: Worby
authors.forename: Charles R
authors.initials: CR
authors.lastname: Ashby
authors.forename: Christian
authors.initials: C
authors.lastname: Heidbreder
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003198:Computer Simulation; D015195:Drug Design; D006168:Guinea Pigs; D006586:Hexanes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D023421:Models, Animal; D008956:Models, Chemical; D015394:Molecular Structure; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D006586:Hexanes; D050637:Receptors, Dopamine D3