2-(3,4-Dihydro-1H-isoquinolin-2yl)-pyridines as a novel class of NR1/2B subtype selective NMDA receptor antagonists.
Recently, we disclosed 4-aminoquinolines as structurally novel NR1/2B subtype selective NMDA receptor antagonists. We would now like to report our findings on structurally related pyridine analogues. The SAR developed in this series resulted in the discovery of high affinity antagonists which are selective (vs alpha1 and M1 receptors) and active in vivo.
Büttelmann
Bernd
B
Pharma Division, Discovery Chemistry, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland. bernd.buettelmann@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
D000161:Acoustic Stimulation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000209:etiology / Q000517:prevention & control; D013329:Structure-Activity Relationship
D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; C409466:NR1 NMDA receptor; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate