title: Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA. litiger_99@yahoo.com
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jaimie K
authors.initials: JK
authors.lastname: Rueter
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chen
authors.forename: Manisha
authors.initials: M
authors.lastname: Moorjani
authors.forename: Marion C
authors.initials: MC
authors.lastname: Lanier
authors.forename: Emily
authors.initials: E
authors.lastname: Lin
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Gross
authors.forename: John E
authors.initials: JE
authors.lastname: Tellew
authors.forename: John P
authors.initials: JP
authors.lastname: Williams
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Lechner
authors.forename: Stacy
authors.initials: S
authors.lastname: Markison
authors.forename: Tanya
authors.initials: T
authors.lastname: Joswig
authors.forename: Siobhan
authors.initials: S
authors.lastname: Malany
authors.forename: Mark
authors.initials: M
authors.lastname: Santos
authors.forename: Julio C
authors.initials: JC
authors.lastname: Castro-Palomino
authors.forename: María I
authors.initials: MI
authors.lastname: Crespo
authors.forename: Maria
authors.initials: M
authors.lastname: Prat
authors.forename: Silvia
authors.initials: S
authors.lastname: Gual
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Díaz
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Slee
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000284:Administration, Oral; D000818:Animals; D000978:Antiparkinson Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006220:Haloperidol / Q000633:toxicity; D006801:Humans; D015394:Molecular Structure; D010300:Parkinson Disease / Q000503:physiopathology*; D010642:Phenoxyacetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D010642:Phenoxyacetates; D011743:Pyrimidines; D003577:Cytochrome P-450 Enzyme System; C465260:Cyp3a2 protein, rat; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D006220:Haloperidol