title: Discovery and optimization of potent and selective functional antagonists of the human adenosine A2B receptor.
abstract: We herein report the discovery of a novel class of antagonists of the human adenosine A2B receptor. This low molecular weight scaffold has been optimized to offer derivatives with potential utility for the alleviation of conditions associated with this receptor subtype, such as nociception, diabetes, asthma and COPD. Furthermore, preliminary pharmacokinetic analysis has revealed compounds with profiles suitable for either inhaled or systemic routes of administration.
authors.affiliation: Vernalis (R&D) Ltd, Granta Park, Cambridge, CB21 6GB, UK.
authors.forename: Simon T
authors.initials: ST
authors.lastname: Bedford
authors.forename: Karen R
authors.initials: KR
authors.lastname: Benwell
authors.forename: Teresa
authors.initials: T
authors.lastname: Brooks
authors.forename: Ijen
authors.initials: I
authors.lastname: Chen
authors.forename: Mike
authors.initials: M
authors.lastname: Comer
authors.forename: Sarah
authors.initials: S
authors.lastname: Dugdale
authors.forename: Tim
authors.initials: T
authors.lastname: Haymes
authors.forename: Allan M
authors.initials: AM
authors.lastname: Jordan
authors.forename: Guy A
authors.initials: GA
authors.lastname: Kennett
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Knight
authors.forename: Burkhard
authors.initials: B
authors.lastname: Klenke
authors.forename: Loic
authors.initials: L
authors.lastname: LeStrat
authors.forename: Angela
authors.initials: A
authors.lastname: Merrett
authors.forename: Anil
authors.initials: A
authors.lastname: Misra
authors.forename: Sean
authors.initials: S
authors.lastname: Lightowler
authors.forename: Anthony
authors.initials: A
authors.lastname: Padfield
authors.forename: Karine
authors.initials: K
authors.lastname: Poullennec
authors.forename: Mark
authors.initials: M
authors.lastname: Reece
authors.forename: Heather
authors.initials: H
authors.lastname: Simmonite
authors.forename: Melanie
authors.initials: M
authors.lastname: Wong
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yule
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; C476003:thienopyrimidine