Potent and Orally Bioavailable 8-Bicyclo[2.2.2]octylxanthines as Adenosine A1 Receptor Antagonists

Author:

Kiesman William F.1,Zhao Jin1,Conlon Patrick R.1,Dowling James E.1,Petter Russell C.1,Lutterodt Frank1,Jin Xiaowei1,Smits Glenn1,Fure Mary1,Jayaraj Andrew1,Kim John1,Sullivan Gail1,Linden Joel1

Affiliation:

1. Departments of Chemistry, Pharmacology, Pharmaceutical Development, and Preclinical Development, Biogen Idec, Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, and Departments of Medicine (Cardiology) and Pharmacology, University of Virginia Medical Center, Charlottesville, Virginia 22901

Publisher

American Chemical Society (ACS)

Subject

Drug Discovery,Molecular Medicine

Reference30 articles.

1. Ray, C. J.; Marshall, J. M. The cellular mechanisms by which adenosine evokes release of nitric oxide from rat aortic endothelium.J. Physiol.2006,570, 85−96. Phillis, J. W. Adenosine and adenine nucleotides as regulators of cerebral blood flow:  Roles of acidosis, cell swelling, and KATP channels.Crit. Rev. Neurobiol.2004,16, 237−270. Turner, C. P.; Seli, M.; Ment, L.; Stewart, W.; Yan, H.; Johansson, B.; Fredholm, B. B.; Blackburn, M.; Rivkees, S. A. A1adenosine receptors mediate hypoxia-induced ventriculomegaly.Proc. Natl. Acad. Sci. U.S.A.2003,100, 11718−11722. Frenguelli, B. G.; Llaudet, E.; Dale, N. High-resolution real-time recording with microelectrode biosensors reveals novel aspects of adenosine release during hypoxia in rat hippocampal slices.J. Neurochem.2003,86, 1506−1515. Sullivan, G. W.; Linden, J. The role of adenosine in tissue protection during ischemia-reperfusion. InSensing, signaling and celladaptation; Storey, K. B., Storey, J. M., Eds.; Elsevier Science B.V.  Amsterdam, The Netherlands, 2002; pp 47−59. Gao, E.; Kaplan, J. L.; Shi, Y.; Victain, M.; Dalsey, W. C.; De Garavilla, L.J. Cardiovasc. Pharmacol.2001,38, 384−394.

2. Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor

3. Structure and function of A 1 adenosine receptors 1

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