title: A new orally bioavailable dual adenosine A2B/A3 receptor antagonist with therapeutic potential.
abstract: The synthesis and SAR of 5-heterocycle-substituted aminothiazole adenosine receptor antagonists is described. Several compounds show high affinity and selectivity for the A2B and A3 receptors. One compound (5f) shows good ADME properties in the rat and as such may be an important new compound in testing the current hypotheses proposing a therapeutic role for a dual A2B/A3 antagonist in allergic diseases.
authors.affiliation: Novartis Institutes for Biomedical Research, Respiratory Diseases Area, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK. neil.press@novartis.com
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Press
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Taylor
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fullerton
authors.forename: Pamela
authors.initials: P
authors.lastname: Tranter
authors.forename: Clive
authors.initials: C
authors.lastname: McCarthy
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Keller
authors.forename: Lyndon
authors.initials: L
authors.lastname: Brown
authors.forename: Robert
authors.initials: R
authors.lastname: Cheung
authors.forename: Julie
authors.initials: J
authors.lastname: Christie
authors.forename: Sandra
authors.initials: S
authors.lastname: Haberthuer
authors.forename: Julia D I
authors.initials: JD
authors.lastname: Hatto
authors.forename: Mark
authors.initials: M
authors.lastname: Keenan
authors.forename: Mark K
authors.initials: MK
authors.lastname: Mercer
authors.forename: Nicola E
authors.initials: NE
authors.lastname: Press
authors.forename: Helene
authors.initials: H
authors.lastname: Sahri
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Tuffnell
authors.forename: Morris
authors.initials: M
authors.lastname: Tweed
authors.forename: John R
authors.initials: JR
authors.lastname: Fozard
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D006571:Heterocyclic Compounds; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D013844:Thiazoles