The discovery of a selective, high affinity A(2B) adenosine receptor antagonist for the potential treatment of asthma.
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).
Zablocki
Jeff
J
Department of Bioorganic Chemistry, CV Therapeutics, Inc., 3172 Porter Dr., Palo Alto, CA 94304, USA. jeff.zablocki@cvt.com
Kalla
Rao
R
Perry
Thao
T
Palle
Venkata
V
Varkhedkar
Vaibhav
V
Xiao
Dengming
D
Piscopio
Anthony
A
Maa
Tenning
T
Gimbel
Art
A
Hao
Jia
J
Chu
Nancy
N
Leung
Kwan
K
Zeng
Dewan
D
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
D058917:Adenosine A2 Receptor Antagonists; D014970:Xanthines