1;Introduction to Adenosine Receptors as Therapeutic Targets;14 1.1;1 Introduction;17 1.2;2 Sources and Fate of Extracellular Adenosine;20 1.3;3 Adenosine Receptor Structure;21 1.4;4 Regulation of Adenosine Receptors;23 1.5;5 Adenosine Receptor Agonists and Antagonists in Preclinical and Clinical Trials;23 1.5.1;5.1 Adenosine Receptor Agonists;24 1.5.2;5.2 Adenosine Receptor Antagonists;26 1.5.3;5.3 Radioligands for In Vivo Imaging;29 1.6;6 Allosteric Modulation of Adenosine Receptors;30 1.7;7 Genetic Deletion of Adenosine Receptors;31 1.8;8 Conclusions;31 1.9;References;32 2;A1 Adenosine Receptor Antagonists, Agonists, and Allosteric Enhancers;38 2.1;1 Introduction;41 2.2;2 A1 Adenosine Receptor Antagonists;41 2.2.1;2.1 KW3902;42 2.2.2;2.2 BG9928;50 2.2.3;2.3 SLV320;56 2.3;3 A1 Adenosine Receptor Agonists;58 2.3.1;3.1 Intravenous Antiarrhythmic Agents: Tecadenoson, Selodenoson, Phenylsulfide, Phenylethers, PJ-875;60 2.3.2;3.2 Insulin-Sensitizing Agents: GR79236, ARA, CVT-3619;62 2.3.3;3.3 Angina Agents: Capadenoson (Nonnucleoside: BAY 68--4986);65 2.4;4 Allosteric Enhancers;65 2.4.1;4.1 Neuropathic Pain: T-62;65 2.5;5 Conclusion;66 2.6;References;67 3;Recent Developments in Adenosine A2A Receptor Ligands;72 3.1;1 Adenosine A2A Receptor Agonists;73 3.1.1;1.1 Adenosine;73 3.1.2;1.2 Ribose-Modified Adenosine Derivatives;76 3.1.3;1.3 Purine-Modified Adenosine Derivatives;77 3.1.3.1;1.3.1 2- or N6-Substituted Adenosine Derivatives;78 3.1.4;1.4 Ribose- and Purine-Modified Adenosine Derivatives;80 3.1.4.1;1.4.1 2-Substituted NECA Derivatives;80 3.1.4.2;1.4.2 Ribose- and Purine-Modified NECA Derivatives;83 3.1.5;1.5 Agonist Radioligands;84 3.1.6;1.6 Partial Agonists;84 3.2;2 Adenosine A2A Receptor Antagonists;85 3.2.1;2.1 Xanthine Derivatives;86 3.2.2;2.2 Adenine Derivatives and Related Heterocyclic Compounds;91 3.2.3;2.3 Heterocyclic Compounds Unrelated to Adenine or Xanthine;97 3.2.4;2.4 Antagonist Radioligands;97 3.3;References;99 4;Recent Developments in A2B Adenosine Receptor Ligands;112 4.1;1 Introduction;114 4.2;2 A2B Adenosine Receptor Antagonists;115 4.2.1;2.1 Xanthine-Based Antagonists;115 4.2.2;2.2 Deazaxanthine-Based Antagonists;122 4.2.3;2.3 Adenine-Based Antagonists;124 4.2.4;2.4 2-Aminopyridine-Based Antagonists;125 4.2.5;2.5 Bipyrimidine-Based Antagonists;126 4.2.6;2.6 Pyrimidone-Based Antagonists;127 4.2.7;2.7 Imidazopyridine-Based Antagonists;127 4.2.8;2.8 Pyrazine-Based Antagonists;128 4.2.9;2.9 Pyrazolo-Triazolo-Pyrimidine-Based Antagonists;131 4.3;3 Conclusion;132 4.4;References;132 5;Medicinal Chemistry of the A3 Adenosine Receptor: Agonists, Antagonists, and Receptor Engineering;136 5.1;1 Introduction;139 5.2;2 A3AR Agonists;141 5.2.1;2.1 Substitution of the Adenine Moiety of Adenine Nucleosides;145 5.2.1.1;2.1.1 N6 Position;145 5.2.1.2;2.1.2 Adenine 2 Position;147 5.2.2;2.2 Ribose Modifications;148 5.2.2.1;2.2.1 Modification of Ribose Hydroxyl Groups;148 5.2.2.2;2.2.2 Modification of the Pentose Ring;149 5.2.3;2.3 Nonadenine Nucleosides and Nonnucleosides as A3AR Agonists;151 5.2.4;2.4 Further Optimization of A3AR Agonists Using Multiple Modifications;151 5.3;3 A3AR Antagonists;152 5.3.1;3.1 Recent Developments in Nonpurine Heterocycles;154 5.3.1.1;3.1.1 Thiazole and Thiadiazole;154 5.3.1.2;3.1.2 Pyrazoloquinolines;155 5.3.1.3;3.1.3 Triazoloquinoxalines;155 5.3.1.4;3.1.4 Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines;156 5.3.1.5;3.1.5 Various Heterocycles;158 5.3.2;3.2 Purine Derivatives;159 5.3.2.1;3.2.1 Adenines;159 5.3.2.2;3.2.2 Triazolopurines;160 5.3.2.3;3.2.3 Tricyclic Xanthines;160 5.3.3;3.3 Nucleoside-Derived A3AR Antagonists;162 5.4;4 Engineering of the A3AR to Avoid Side Effects of Conventional Synthetic Agonists;164 5.5;5 Conclusions;164 5.6;References;165 6;Adenosine Receptors and the Heart: Role in Regulation of Coronary Blood Flow and Cardiac Electrophysiology;173 6.1;1 General Background: The Adenosine Hypothesis;176 6.2;2 Adenosine and Coronary Regulation;177 6.3;3 Endothelium-Dependent and E