title: Synthesis and SAR studies of trisubstituted purinones as potent and selective adenosine A2A receptor antagonists.
abstract: A series of trisubstituted purinones was synthesized and evaluated as A(2A) receptor antagonists. The A(2A) structure-activity relationships at the three substituted positions were studied and selectivity against the A(1) receptor was investigated. One antagonist 12o exhibits a K(i) of 9nM in an A(2A) binding assay, a K(b) of 18nM in an A(2A) cAMP functional assay, and is 220-fold selective over the A(1) receptor.
authors.affiliation: Pharmacopeia, Inc., PO Box 5350, Princeton, NJ 08543, USA.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Shao
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Cole
authors.forename: Marc-Raleigh
authors.initials: MR
authors.lastname: Brescia
authors.forename: Lan-Ying
authors.initials: LY
authors.lastname: Qin
authors.forename: Jingqi
authors.initials: J
authors.lastname: Duo
authors.forename: Tara M
authors.initials: TM
authors.lastname: Stauffer
authors.forename: Laura L
authors.initials: LL
authors.lastname: Rokosz
authors.forename: Brian F
authors.initials: BF
authors.lastname: McGuinness
authors.forename: Ian
authors.initials: I
authors.lastname: Henderson
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D006801:Humans; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011688:Purinones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011688:Purinones; D043705:Receptor, Adenosine A2A; D011994:Recombinant Proteins