Discovery of (R)-1-[2-hydroxy-3-(4-hydroxy-phenyl)-propyl]-4-(4-methyl-benzyl)-piperidin-4-ol: a novel NR1/2B subtype selective NMDA receptor antagonist.
Starting from Ro-25-6981 as a lead compound, highly potent and selective NR1/2B subtype selective NMDA receptor antagonists, with low activity at alpha(1) adrenergic receptors were developed.
Pinard
E
E
Pharma Division, Discovery Chemistry, F. Hoffmann-La Roche Ltd., CH-4070, Basel, Switzerland. emmanuel.pinard@roche.com
Alanine
A
A
Bourson
A
A
Büttelmann
B
B
Gill
R
R
Heitz
M
M
Jaeschke
G
G
Mutel
V
V
Trube
G
G
Wyler
R
R
D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
C435645:1-(2-hydroxy-3-(4-hydroxy-phenyl)-propyl)-4-(4-methyl-benzyl)-piperidin-4-ol; D018691:Excitatory Amino Acid Antagonists; D010636:Phenols; D010880:Piperidines; D018340:Receptors, Adrenergic, alpha-1; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981