Triazolyl azabicyclo[3.1.0]hexanes: A class of potent and selective dopamine D(3) receptor antagonists.
Herein we report a detailed description of the structure-activity relationships for a novel series of "C-linked" 1,2,4-triazolylazabicyclo[3.1.0]hexanes. These derivatives are endowed with very high in vitro affinity and selectivity for the dopamine D(3) receptor. An optimization with respect to undesired affinity toward the hERG potassium channel is also reported. Members of this compound series also show excellent in vitro and in vivo pharmacokinetic properties.
Neurosciences Centre of Excellence, Verona, Italy.
Giorgio
G
Bonanomi
Simone
S
Braggio
Anna Maria
AM
Capelli
Anna
A
Checchia
Romano
R
Di Fabio
Carla
C
Marchioro
Luca
L
Tarsi
Giovanna
G
Tedesco
Silvia
S
Terreni
Angela
A
Worby
Christian
C
Heibreder
Fabrizio
F
Micheli
D000818:Animals; D001372:Aza Compounds / Q000737:chemistry*; D001665:Binding Sites; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D003198:Computer Simulation; D006586:Hexanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D006586:Hexanes; D050637:Receptors, Dopamine D3; D014230:Triazoles