Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists

A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's diseas...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2008-03, Vol.18 (6), p.1778-1783
Main Authors: XIAOHU ZHANG, RUETER, Jaimie K, MARKISON, Stacy, JOSWIG, Tanya, MALANY, Siobhan, SANTOS, Mark, CASTRO-PALOMINO, Julio C, CRESPO, Maria I, PRAT, Maria, GUAL, Silvia, DIAZ, José-Luis, SAUNDERS, John, YONGSHENG CHEN, SLEE, Deborah H, MOORJANI, Manisha, LANIER, Marion C, LIN, Emily, GROSS, Raymond S, TELLEW, John E, WILLIAMS, John P, LECHNER, Sandra M
Format: Article
Language:English
Subjects:
Adenosine A2 Receptor Antagonists
Administration, Oral
Animals
Anticonvulsants. Antiepileptics. Antiparkinson agents
Antiparkinson Agents - chemical synthesis
Antiparkinson Agents - pharmacology
Biological and medical sciences
Catalepsy - chemically induced
Catalepsy - prevention & control
Cytochrome P-450 CYP2D6 - metabolism
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System - metabolism
Electrophysiology
Ether-A-Go-Go Potassium Channels - antagonists & inhibitors
Haloperidol - toxicity
Humans
Medical sciences
Molecular Structure
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Parkinson Disease - physiopathology
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Phenoxyacetates - chemical synthesis
Phenoxyacetates - chemistry
Phenoxyacetates - pharmacology
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - pharmacology
Rats
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2008.02.032