title: Synthesis and evaluation of two series of 4'-aza-carbocyclic nucleosides as adenosine A2A receptor agonists.
abstract: The synthesis of two series of 4'-aza-carbocyclic nucleosides are described in which the 4'-substituent is either a reversed amide, relative to the carboxamide of NECA, or an N-bonded heterocycle. Using established purine substitution patterns, potent and selective examples of agonists of the human adenosine A(2A) receptor have been identified from both series. The propionamides 14-18 and the 4-hydroxymethylpyrazole 32 were determined to be the most potent and selective examples from the 4'-reversed amide and 4'-N-bonded heterocyclic series, respectively.
authors.affiliation: Novartis Institutes for BioMedical Research, Respiratory Diseases Area, Horsham, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Beattie
authors.forename: Andrew
authors.initials: A
authors.lastname: Brearley
authors.forename: Zarin
authors.initials: Z
authors.lastname: Brown
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Charlton
authors.forename: Brian
authors.initials: B
authors.lastname: Cox
authors.forename: Robin A
authors.initials: RA
authors.lastname: Fairhurst
authors.forename: John R
authors.initials: JR
authors.lastname: Fozard
authors.forename: Peter
authors.initials: P
authors.lastname: Gedeck
authors.forename: Paul
authors.initials: P
authors.lastname: Kirkham
authors.forename: Koremu
authors.initials: K
authors.lastname: Meja
authors.forename: Lana
authors.initials: L
authors.lastname: Nanson
authors.forename: James
authors.initials: J
authors.lastname: Neef
authors.forename: Helen
authors.initials: H
authors.lastname: Oakman
authors.forename: Gillian
authors.initials: G
authors.lastname: Spooner
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Taylor
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Turner
authors.forename: Ryan
authors.initials: R
authors.lastname: West
authors.forename: Hannah
authors.initials: H
authors.lastname: Woodward
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D016466:CHO Cells; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011742:Pyrimidine Nucleotides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D001372:Aza Compounds; D002264:Carboxylic Acids; D009705:Nucleosides; D011742:Pyrimidine Nucleotides; D043705:Receptor, Adenosine A2A