4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor antagonists.
A series of 4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and analogous quinolines was prepared and evaluated as NR1/2B subtype selective NMDA receptor antagonists. 2-Hydroxyalkylamino substitution combines high affinity with selectivity (vs alpha1 and M1 receptors) and activity in vivo.
Büttelmann
Bernd
B
Pharma Division, Discovery Chemistry, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland. bernd.buttelmann@roche.com
Alanine
Alexander
A
Bourson
Anne
A
Gill
Ramanjit
R
Heitz
Marie-Paule
MP
Mutel
Vincent
V
Pinard
Emmanuel
E
Trube
Gerhard
G
Wyler
René
R
D000818:Animals; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship
C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D011725:Pyridines; D011804:Quinolines; D016194:Receptors, N-Methyl-D-Aspartate