Fused aminotetralins: novel antagonists with high selectivity for the dopamine D3 receptor.
Starting from a series of 2-aminotetralins 1, a novel series of N-[4-(4-phenylbenzoylamino)butyl]-octahydrobenzoquinolines and hexahydrobenzoindoles with high potency and selectivity for the dopamine D3 receptor has been designed. The effect of ligand chirality on binding affinity has been established. Selected derivatives (e.g. 2o, 2p) show high functional selectivity and enhanced in vivo properties compared to 1.
Avenell
K Y
KY
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.
Boyfield
I
I
Coldwell
M C
MC
Hadley
M S
MS
Healy
M A
MA
Jeffrey
P M
PM
Johnson
C N
CN
Nash
D J
DJ
Riley
G J
GJ
Scott
E E
EE
Smith
S A
SA
Stacey
R
R
Stemp
G
G
Thewlis
K M
KM
D000818:Animals; D065127:Dopamine D2 Receptor Antagonists; D008657:Metabolic Clearance Rate; D051381:Rats; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C006561:2-aminotetralin