The discovery of a selective, high affinity A(2B) adenosine receptor antagonist for the potential treatment of asthma

Jeff Zablocki; Rao Kalla; Thao Perry; Venkata Palle; Vaibhav Varkhedkar; Dengming Xiao; Anthony Piscopio; Tenning Maa; Art Gimbel; Jia Hao; Nancy Chu; Kwan Leung; Dewan Zeng

doi:10.1016/j.bmcl.2004.11.044

The discovery of a selective, high affinity A(2B) adenosine receptor antagonist for the potential treatment of asthma

Bioorg Med Chem Lett. 2005 Feb 1;15(3):609-12. doi: 10.1016/j.bmcl.2004.11.044.

Authors

Jeff Zablocki¹, Rao Kalla, Thao Perry, Venkata Palle, Vaibhav Varkhedkar, Dengming Xiao, Anthony Piscopio, Tenning Maa, Art Gimbel, Jia Hao, Nancy Chu, Kwan Leung, Dewan Zeng

Affiliation

¹ Department of Bioorganic Chemistry, CV Therapeutics, Inc., 3172 Porter Dr., Palo Alto, CA 94304, USA. jeff.zablocki@cvt.com

PMID: 15664822
DOI: 10.1016/j.bmcl.2004.11.044

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).

MeSH terms

Adenosine A2 Receptor Antagonists*
Asthma / drug therapy*
Drug Stability
Humans
Liver / cytology
Liver / metabolism
Structure-Activity Relationship
Xanthines / chemical synthesis
Xanthines / pharmacology

Substances

Adenosine A2 Receptor Antagonists
Xanthines