Exploration of the amine terminus in a novel series of 1,2,4-triazolo-3-yl-azabicyclo[3.1.0]hexanes as selective dopamine D3 receptor antagonists.
A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes with high affinity and selectivity for the DA D(3) receptor and excellent pharmacokinetic profiles was recently reported. We also recently discussed the role of the linker associated with the triazole moiety. In this manuscript, we are reporting a detailed exploration of the region of the receptor interacting with the amine terminus of the scaffold wherein SAR and developability data associated with these novel templates was undertaken.
Micheli
Fabrizio
F
Neurosciences Centre of Excellence, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. fabrizio.micheli@aptuit.com
Arista
Luca
L
Bertani
Barbara
B
Braggio
Simone
S
Capelli
Anna Maria
AM
Cremonesi
Susanna
S
Di-Fabio
Romano
R
Gelardi
Giacomo
G
Gentile
Gabriella
G
Marchioro
Carla
C
Pasquarello
Alessandra
A
Provera
Stefano
S
Tedesco
Giovanna
G
Tarsi
Luca
L
Terreni
Silvia
S
Worby
Angela
A
Heidbreder
Christian
C
D000818:Animals; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D020134:Catalytic Domain; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D008958:Models, Molecular; D011869:Radioligand Assay; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D053961:Azabicyclo Compounds; D050637:Receptors, Dopamine D3; D014230:Triazoles