title: The discovery of a selective, high affinity A(2B) adenosine receptor antagonist for the potential treatment of asthma.
abstract: Adenosine has been suggested to play a role in asthma, possibly via activation of A(2B) adenosine receptors on mast cells and other pulmonary cells. We describe our initial efforts to discover a xanthine based selective A(2B) AdoR antagonist that resulted in the discovery of CVT-5440, a high affinity A(2B) AdoR antagonist with good selectivity (A(2B) AdoR K(i)=50 nM, selectivity A(1)>200: A(2A)>200: A(3)>167).
authors.affiliation: Department of Bioorganic Chemistry, CV Therapeutics, Inc., 3172 Porter Dr., Palo Alto, CA 94304, USA. jeff.zablocki@cvt.com
authors.forename: Jeff
authors.initials: J
authors.lastname: Zablocki
authors.forename: Rao
authors.initials: R
authors.lastname: Kalla
authors.forename: Thao
authors.initials: T
authors.lastname: Perry
authors.forename: Venkata
authors.initials: V
authors.lastname: Palle
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Varkhedkar
authors.forename: Dengming
authors.initials: D
authors.lastname: Xiao
authors.forename: Anthony
authors.initials: A
authors.lastname: Piscopio
authors.forename: Tenning
authors.initials: T
authors.lastname: Maa
authors.forename: Art
authors.initials: A
authors.lastname: Gimbel
authors.forename: Jia
authors.initials: J
authors.lastname: Hao
authors.forename: Nancy
authors.initials: N
authors.lastname: Chu
authors.forename: Kwan
authors.initials: K
authors.lastname: Leung
authors.forename: Dewan
authors.initials: D
authors.lastname: Zeng
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D001249:Asthma / Q000188:drug therapy*; D004355:Drug Stability; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D014970:Xanthines