Novel 2,3,4,5-tetrahydro-1H-3-benzazepines with high affinity and selectivity for the dopamine D3 receptor.
Starting from the dopamine D3 receptor antagonist SB-277011 1, a series of 2,3,4,5-tetrahydro-1H-3-benzazepines has been identified with high affinity for the dopamine D3 receptor and selectivity over the D2 receptor. The 3-acetamido-2-fluorocinnamide derivative 20 gave high D3 receptor affinity (pKi 8.4) with 130-fold selectivity over the 2, receptor.
Austin
N E
NE
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.
Avenell
K Y
KY
Boyfield
I
I
Branch
C L
CL
Hadley
M S
MS
Jeffrey
P
P
Johnson
C N
CN
Macdonald
G J
GJ
Nash
D J
DJ
Riley
G J
GJ
Smith
A B
AB
Stemp
G
G
Thewlis
K M
KM
Vong
A K
AK
Wood
M
M
D000818:Animals; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050637:Receptors, Dopamine D3; D044005:Tetrahydroisoquinolines
C493595:Drd3 protein, rat; D009570:Nitriles; D011804:Quinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines