Parallel synthesis of a series of subtype-selective NMDA receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 6, 2000, Pages 527-529

  Gregory, Tracy F ^a   Wright, Jon L ^a   Wise, Lawrence D ^a   Meltzer, Leonard T ^a   Serpa, Kevin A ^a   Konkoy, Christopher S ^b   Whittemore, Edward R ^b   Woodward, Richard M ^b  

^a PFIZER INC   (United States)

^b Department of Pharmacokinetics and Drug Metabolism   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 HETEROARYLTHIOALKYL 4 BENZYLPIPERIDINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PIPERIDINE DERIVATIVE; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG;

ANIMAL MODEL; ARTICLE; CHEMICAL MODIFICATION; DRUG POTENCY; DRUG SYNTHESIS; HYDROGEN BOND; NONHUMAN; PARKINSON DISEASE; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; EXCITATORY AMINO ACID ANTAGONISTS; OXIDOPAMINE; PIPERIDINES; RATS; RECEPTORS, N-METHYL-D-ASPARTATE; STRUCTURE-ACTIVITY RELATIONSHIP; SYMPATHECTOMY, CHEMICAL; SYMPATHOLYTICS;

ANIMALIA;

EID: 0034689520     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00035-4     Document Type: Article

References (5)

1. Cooper A.J., Carroll C.B., Mitchell I.J. CNS Drugs. 9:1998;421.
2. All compounds were tested for inhibitory activity at NR1A/2A, NR1A/2B and NR1A/2C receptors in frog oocytes as previously described. Values are mean SEM taken from 1 to 4 experiments, as noted in parentheses: Wright, J. L.; Gregory, T. F.; Bigge, C. F.; Boxer, P. A.; Serpa, K.; Meltzer, L. T.; Wise, L. D.; Cai, S. X.; Hawkinson, J.; Whittemore, E.; Woodward, R.; Zhou, Z. J. Med. Chem. 1999, 42, 2469.
3. 6-OHDA rat model: rats were lesioned by injection of 6-hydroxydopamine into the right medial forebrain bundle rostral to the substantia nigra. After lesioning, rats are conditioned with L-DOPA methyl ester (10 mg/kg SC, mixed with s-carbidopa 1 mg/kg to prevent peripheral decarboxylation) to establish a stable response. Vehicle or the test compound was administered orally at the same time as L-DOPA in a randomized, crossover manner, with 1 week between treatments. The total number of contraversive rotations observed following dosing with the test compound+L-DOPA was compared with the response in the same rats to vehicle+L-DOPA, using a paired t-test.
4. Mistry M., Houston J.B. Drug Metab. Dispos. 13:1985;740.
5. 1H NMR, IR, MS and microanalysis.