title: Synthesis and pharmacological evaluation of dual acting antioxidant A(2A) adenosine receptor agonists.
abstract: A series of adenosine-5'-N-alkylcarboxamides and N(6)-(2,2-diphenylethyl)adenosine-5'-N-alkylcarboxamides bearing antioxidant moieties in the 2-position were synthesized from the versatile intermediate, O(6)-(benzotriazol-1-yl)-2-fluoro-2',3'-O-isopropylideneinosine-5'-N-alkylcarboxamide (1). These compounds were evaluated as A(2A) adenosine receptor (A(2A)R) agonists in a cAMP accumulation assay, and a number of potent and selective agonists were identified. Three of these compounds were evaluated further in an ischemic injury cell survival assay and a reactive oxygen species (ROS) production assay whereby 15b and 15c were shown to reduce ROS activity and cell death due to ischemia.
authors.affiliation: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Hausler
authors.forename: Shane M
authors.initials: SM
authors.lastname: Devine
authors.forename: Fiona M
authors.initials: FM
authors.lastname: McRobb
authors.forename: Lyndon
authors.initials: L
authors.lastname: Warfe
authors.forename: Colin W
authors.initials: CW
authors.lastname: Pouton
authors.forename: John M
authors.initials: JM
authors.lastname: Haynes
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bottle
authors.forename: Paul J
authors.initials: PJ
authors.lastname: White
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scammells
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D016466:CHO Cells; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D008958:Models, Molecular; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D015427:Reperfusion Injury / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000577:Amides; D000975:Antioxidants; D017382:Reactive Oxygen Species; D043705:Receptor, Adenosine A2A; D000242:Cyclic AMP; D000241:Adenosine