Discovery of subtype-selective NMDA receptor ligands: 4-benzyl-1-piperidinylalkynylpyrroles, pyrazoles and imidazoles as NR1A/2B antagonists.
4-Benzyl-1-[4-(1H-imidazol-4-yl)but-3-ynyl]piperidine (8) has been identified as a potent antagonist of the NR1A/2B subtype of the NMDA receptor. When dosed orally, this compound potentiates the effects of L-DOPA in the 6-hydroxydopamine-lesioned rat, a model of Parkinson's disease.
Wright
J L
JL
Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Gregory
T F
TF
Boxer
P A
PA
Meltzer
L T
LT
Serpa
K A
KA
Wise
L D
LD
D000818:Animals; D004195:Disease Models, Animal; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007980:Levodopa / Q000819:agonists / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
C401406:4-benzyl-1-(4-(1H-imidazol-4-yl)but-3-ynyl)piperidine; D007093:Imidazoles; D008024:Ligands; C121001:NR2B NMDA receptor; D010880:Piperidines; D011720:Pyrazoles; D011758:Pyrroles; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D016627:Oxidopamine