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.
Bonanomi
Giorgio
G
Neurosciences Centre of Excellence, Verona, Italy.
Braggio
Simone
S
Capelli
Anna Maria
AM
Checchia
Anna
A
Di Fabio
Romano
R
Marchioro
Carla
C
Tarsi
Luca
L
Tedesco
Giovanna
G
Terreni
Silvia
S
Worby
Angela
A
Heibreder
Christian
C
Micheli
Fabrizio
F
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