Therapeutic potential of A1 adenosine receptor ligands: A survey of recent patent literature

Expert Opinion on Therapeutic Patents

Volumn 18, Issue 7, 2008, Pages 677-691

  Giorgi, Irene ^a   Nieri, Paola ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

A1 adenosine receptot; Agonists; Antagonists; Asthma; Bone loss; Cardiac arrhythmia; Cardioprotection; CNS disorders; Diabetes; Enhancers; Insulin resistance; Kidney protection; Obesity; Pain; Partial agonists; Sepsis

Indexed keywords

2 AMINO 3 AROYLTHIOPHENE DERIVATIVE; 2 AMINO 3 BENZOYLTHIOPHENE DERIVATIVE; 6 N (2 HYDROXYCYCLOPENTYL)ADENOSINE; 8 CYCLOPENTYL 1,3 DIPROPYLXANTHINE; 8 PYRAZOL 9 ALKYLADENINE DERIVATIVE; 9 ALKYL 6 N CYCLOALKYL 8 ARYLADENINE; ADENINE DERIVATIVE; ADENOSINE; ADENOSINE A1 RECEPTOR; ADENOSINE A1 RECEPTOR AGONIST; ADENOSINE A1 RECEPTOR ANTAGONIST; ADENOSINE DERIVATIVE; ADENOSINE RECEPTOR AFFECTING AGENT; ADENOSINE RECEPTOR BLOCKING AGENT; AMINOPYRROLOPYRIMIDINE; ANTIARRHYTHMIC AGENT; BAY 68 4986; CAPADENOSON; CVT 2759; CVT 3619; GW 493838; METHANOCARBA ADENINE NUCLEOSIDE DERIVATIVE; PYRAZOLOPYRIDINE DERIVATIVE; PYRIDINE DERIVATIVE; PYRROLOPYRIMIDINE DERIVATIVE; RG 14202; SELODENOSON; SLV 320; TECADENOSON; THIOPHENE DERIVATIVE; UNINDEXED DRUG; XANTHINE DERIVATIVE;

ALLOSTERISM; AMINO ACID SUBSTITUTION; CARDIOVASCULAR DISEASE; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; DIABETES MELLITUS; DRUG ACTIVITY; DRUG MARKETING; DRUG MECHANISM; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; DYSPNEA; FLUSHING; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART PROTECTION; HUMAN; HYPOTENSION; INSULIN RESISTANCE; KIDNEY DISEASE; KIDNEY FAILURE; LIPOLYSIS; NEPHROTOXICITY; NEUROPATHIC PAIN; NEUROPROTECTION; NONHUMAN; OBESITY; OSTEOPENIA; OSTEOPOROSIS; PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA; PATENT; RECEPTOR AFFINITY; RESPIRATORY TRACT DISEASE; REVIEW; SEPSIS; SIDE EFFECT; THORAX PAIN; TISSUE SPECIFICITY;

EID: 48049090480     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.18.7.677     Document Type: Review

References (140)

1. 1 adenosine receptor. Biochem Biophys Res Commun 1992;187(2):919-26
2. Fredholm BB, Ijzerman AP, Jacobson KA, et al. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 2001;53:527-52
3. Soudijn W, Van Wijngaarden I, Ijzerman AP. Medicinal chemistry of adenosine A1 receptor ligands. Curr Top Med Chem 2003;3:355-67
4. Dhalla AK, Shryock JC, Shreeniwas R, Belardinelli L. Pharmacology and therapeutic applications of A1 adenosine receptor ligands. Curr Top Med Chem 2003;3:369-85
5. Zablocki J, Elzein E, Organ MG, et al. Partial and full agonists of Al adenosine receptors. WO2006026651; 2006
6. Dhalla AK, Santikul M, Smith M, et al. Antilipolytic activity of a novel partial A1 adenosine receptor agonist devoid of cardiovascular effects: comparison with nicotinic acid. J Pharmacol Exp Ther 2007;32(1):327-33
7. Fatholahi M, Xiang Y, Wu Y, et al. A novel partial agonist of the A1;-adenosine receptor and evidence of receptor homogeneity in adipocytes. J Pharmacol Exp Ther 2006;317(2):676-84
8. ELzein E, Ibrahim P, Palle V, et al. Preparation of nucleosides as partial and full agonists of Al adenosine receptors. US2005020532;2005
9. Dhalla A, Elzein E, Ibrahim P, et al. Preparation of nucleosides as partial and full agonists of Al adenosine receptors. US2007185051;2007
10. Zablocky J, Palle V, Elzein E, Li X. Partial and full agonists of A1 adenosine receptors. WO2004016635; 2004
11. Zablocky J, Palle V, Elzein E, Li X. Partial and full agonists of A1 adenosine receptors. US20060135467;2006
12. 1 adenosine receptor agonists. WO2006125211; 2006
13. 1 receptor agonists. Bioorg Med Chem Lett 2007;17(1):161-6
14. Elzein E, Kalla R, Perry T, et al. A1 adenosine receptor agonists. WO2006125190; 2006
15. Jagtap P, Szabo C, Salzman A. Purine derivatives as adenosine A1 receptor agonists and methods of use thereof. WO2005117910; 2005
16. Jagtap P, Salzman A. purine derivatives and methods of use thereof. WO2007064795;2007
17. Jagtap P, Salzman A. Purine derivatives and methods of use thereof. WO2007111954; 2007
18. Elzein E, Li X, Zablocky J. A1 adenosine receptor agonists. US2007087994; 2007
19. Gumina G, Beeson C, Wright G. L-nucleosides as ligands to adenosine receptors. US2007054875; 2007
20. Jacobson K, Joshi B, Tchilibon S. Purine derivatives as A3 and A1 adenosine receptor agonists. WO2006031505; 2006
21. Rosentreter U, Kraemer T, Shimada M, et al. Substituted 2-thio-3,5-dicyano-4- phenyl-6-aminopyridines and the use of the same. WO2003053441; 2003
22. Freiberg C, Knezevic I, Krahn T, et al. Use of adenosine A1 receptor agonists for the protection of renal cells against toxic effects caused by aminoglycosides during treatment of infectious diseases. WO2007073855; 2007
23. Baraldi PG, Fruttarolo F, Tabrizi MA, et al. Novel 8-heterocyclyl xanthine derivatives in drug development: an update. Expert Opin Drug Discov 2007;2(9):1161-83
24. Moro S, Gao ZG, Jacobson KA, Spalluto G. Progress in the pursuit of therapeutic adenosine receptor antagonists. Med Res Rev 2006;26:131-59
25. Yuzlenko O, Kiec-Kononowicz K. Potent adenosine A1 and A2A receptors antagonists: recent developments. Curr Med Chem 2006;13(30):3609-25
26. Jacobson KA, Cao ZG. Adenosine receptors as therapeutic targets. Nat Rev Drug Discov 2006;5(3):247-64
27. Wilson C, Partridge JJ. A1 adenosine receptor antagonists. WO2005009343;2005
28. Obiefuna PC, Batra VK, Nadeem A, et al. A novel A1 adenosine receptor antagonist (L-97-1) reduces allergic responses to house dust mite in an allergic rabbit model of asthma. J Pharmacol Exp Ther 2005;315:329-36
29. Minaskanian G, Rippel K. Substituted 9-alkyladenines and the use thereof. WO2006099204;2006
30. Klotz K-N, Kachler S, Lambertucci C, et al. 9-Ethyladenine derivatives as adenosine receptor antagonists: 2- and 8-substitution result in distinct selectivities. Naunyn Schmiedebergs Arch Pharm 2003;367:629-34
31. Cristalli G. A1 adenosine receptor antagonists. US2005245546; 2005
32. Zablocki J, Kalla R. A1 adenosine receptor antagonists. WO2005009445; 2005
33. Akahane A, Kuroda S, Irani H. Pyrazolopyridine as adenosine antagonists. WO0024742; 2000
34. 2A receptor antagonists. WO2004016605; 2004
35. Yonishi S, Aoki S. Pyrazine derivatives and pharmaceutical use thereof. US2005113387; 2005
36. Yonishi S, Aoki S, et al. Pyrazine derivatives and pharmaceutical use thereof. WO2005040151; 2005
37. Tsutsumi H, Tabuchi S, Minagawa M, Akahane A. Pyrazine derivatives and pharmaceutical use thereof. US2005222159; 2005
38. Castelhano A, Mckibben B, Witter DJ. Compounds specific to adenosine A1 receptors and uses thereof. US2004082599; 2004
39. kalk P, Eggert B, Relle K, et al. The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure. Br J Pharmacol 2007;151(7):1025-32
40. Gonzales LL, Camacho GJA. Novel compounds as antagonists for A1 adenosine receptors. WO2007116106; 2007
41. Chang LCW, Ijzerman AP. Pyrimidine derivative as adenosine receptor ligands. WO2005033085; 2005
42. Bruns RF, Fergus JH. Allosteric enhancement of adenosine A1 receptor binding and function by 2-amino-3-benzoylthiophenes. Mol Pharmacol 1990;38:939-49
43. Bruns RE, Fergus JH, Coughenour LL, et al. Structure-activity relationships for enhancement of adenosine A1 receptor binding by 2-amino-3-benzoylthiophenes. Mol Pharmacol 1990;38:950-8
44. Korounakis AP, Van Der Klein PAM, Ijzerman AP. Elucidation of structure-activity relationships of 2-amino-3-benzoylthiophenes: study of their allosteric enhancing vs. antagonistic activity on adenosine A1 receptors. Drug Dev Res 2000;49:227-37
45. Baraldi PG, Zaid AN, Lampronti I, et al. Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor. Bioorg Med Chem Lett 2000;10:1953-7
46. Tramberg CE, Zickgraf A, Giunta BN, et al. 2-Amino-3-aroyl-4,5-alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors. J Med Chem 2002;45:382-9
47. Gao Z-G, Kim S-K, Ijzerman AP, Jacbson KA. Allosteric modulation of the adenosine family of receptors. Mini Rev Med Chem 2005;5:545-53
48. Baraldi PG, Iaconito MA, Moorman AR, et al. Allosteric enhancer for A1 adenosine receptor. Mini Rev Med Chem 2007;7:559-69
49. Baraldi PG. Allosteric adenosine receptor modulators. WO9921617; 1999
50. Baraldi PG. Allosteric adenosine receptor modulators. US2001047008; 2001
51. Linden JM, Olsson RA, Scammells PJ. 2-Amino-3-aroyl-4,5 alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors. US2003078248; 2003
52. De Vry J, Kuhl E, Franken-Kunkel P, Eckel G. Pharmacological characterization of the chronic constriction injury model of neuropathic pain. Eur J Pharmacol 2004;491:137-49
53. Lerman BB, Belardinelli L. Cardiac electrophysiology of adenosine. Basic and clinical concepts. Circulation 1991;83(5):1499-509
54. Song Y, Shryock J C, Knot HJ, Belardinelli L. Selective attenuation by adenosine of arrhythmogenic action of isoproterenol on ventricular myocytes. Am J Physiol Heart Circ Physiol 2001;280(6):H2789-95
55. Hebbar AK, Hueston WJ. Management of common arrhythinias: part I. Supraventricular arrhythmias. Am Fam Physician 2002;65(12):2479-86
56. Strickberger SA, Man KC, Daoud EG, et al. Adenosine-induced atrial arrhythmia: a prospective analysis. Ann Intern Med 1997;127(6):417-22. Erratum: Ann Intern Med 1998;128(6):511
57. Lerman BB, Ellenbogen KA, Kadish A, et al. Electrophysiologic effects of a novel selective adenosine A1 agonist (CVT-510) on atrioventricular nodal conduction in humans. J Cardiovasc Pharmacol Ther 2001;6(3):237-45
58. Peterman C, Sanoski CA. Tecadenoson. a novel, selective A1 adenosine receptor agonist. Cardiol Rev 2005;13(6):315-21
59. Ellenbogen KA, O'Neill G, Prystowsky EN, et al. TEMPEST Study Group. Trial to evaluate the management of paroxysmal supraventricular tachycardia during an electrophysiology study with tecadenoson. Circulation 2005;111(24):3202-8
60. Zaza A. CVT-510 (CV Therapeutics). Curr Opin Investig Drugs 2002;3(1):96-100
61. Merkel LA, Rivera LM, Colussi DJ, et al. In vitro and in vivo characterization of an A1-selective adenosine agonist, RG14202. J Pharmacol Exp Ther 1993;265(2):699-706
62. Gadgil S, Wheeler W. Method of treating atrial fibrillation or atrial flutter. US2005009776; 2005
63. Aurora J, Gill MS, Ong KKH. Controlled release formulation. WO2005025545; 2005
64. NCT00040001. Safety and efficacy study of an A1-adenosine receptor agonist to slow heart rate in atrial fibrillation. Available from: http://clinicaltrials.gov/ct2/show/NCT00040001
65. NCT00568945. Study to investigate the effect of the A1 agonist capadenoson on ventricular hr in patients with persistent or permanent atrial fibrillation. Available from: http://clinicaltrials.gov/ct2/show/ NCT00568945
66. Song Y, Wu L, Shryock JC, Belardinelli L. Selective attenuation of isoproterenol-stimulated arrhythmic activity by a partial agonist of adenosine A1 receptor. Circulation 2002;105(1):118-23
67. Donato M, Gelpi RJ. Adenosine and cardioprotection during reperfusion: an overview. Mol Cell Biochem 2003;251:153-9
68. Headrick JP, Gauthier NS, Morrison RR, Matherne GP. Cardioprotection by K(ATP) channels in wild-type hearts and hearts overexpressing A1;-adenosine receptors. Am J Physiol Heart Circ Physiol 2000;279(4):H1690-7
69. Yang Z, Cerniway RJ, Byford AM, et al. Cardiac overexpression of A1-adenosine receptor protects intact mice against myocardial infarction. Am J Physiol Heart Circ Physiol 2002;282(3):H949-55
70. Lankford AR, yang JN, Rose'meyer R, et al. Effect of modulating cardiac A1 adenosine receptor expression on protection with ischemic preconditioning. Am J Physiol Heart Circ Physiol 2006;290(4):H1469-73
71. Yang Z, Day YJ, Toufektsian MC, et al. Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to its action on CD4+ T lymphocytes. Circulation 2006;114(19):2056-64
72. De Jonge R, Out M, Maas WJ, De Jong JW. Preconditioning of rat hearts by adenosine A1 or A3 receptor activation. Eur J Pharmacol 2002;441(3):165-72
73. Eckle T, Krahn T, Grenz A, et al. Cardioprotection by ecto-5′-nucleotidase (CD73) and A2B adenosine receptors. Circulation 2007;115(12):1581-90
74. Sawynok J, Liu XJ. Adenosine in the spinal cord and periphery: release and regulation of pain. Prog Neurobiol 2003;69(5):313-40
75. Liu XJ, Salter MW. Purines and pain mechanisms: recent developments. Curr Opin Investig Drugs 2005;6(1):65-75
76. Zahn PK, Straub H, Wenk M, Pogatzki-Zahn EM. Adenosine A1 but not A2a receptor agonist reduces hyperalgesia caused by a surgical incision in rats: a pertussis toxin-sensitive G protein-dependent process. Anesthesiology 2007;107(5):797-806
77. Lim WK. GPCR drug discovery: novel ligands for CNS receptors. Recent Patents CNS Drug Discov 2007;2(2):107-12
78. Giffin NJ, Kowacs F, Libri V, et al. Effect of the adenosine A1 receptor agonist GR79236 on trigeminal nociception with blink reflex recordings in healthy human subjects. Cephalalgia 2003;23(4):287-92
79. NCT00376454. The study of GW493838, an adenosine A1 agonist, in peripheral neuropathic pain. Available from: http://clinicaltrials.gov/ ct2/show/NCT00376454
80. NCT00506610. A study to determine if an investigational pain medicine provides relief of chronic pain after a shingles outbreak. Available from: http://clinicaltrials.gov/ct2/show/NCT00506610
81. NCT00298636. Dose-response of adenosine for perioperative pain. Available from: http://clinicaltrials.gov/ct2/show/NCT00298636
82. NCT00349921. Clonidine versus adenosine to treat neuropathic pain. Available from: http://clinicaltrials.gov/ct2/show/NCT00349921
83. Stone TW. Adenosine, neurodegeneration and neuroprotection. Neurol Res 2005;27(2):161-8
84. Ribeiro JA. What can adenosine neuromodulation do for neuroprotection? Curr Drug Targets CNS Neurol Disord 2005;4(4):325-9
85. Benarroch EE. Adenosine and its receptors: multiple modulatory functions and potential therapeutic targets for neurologic disease. Neurology 2008;70(3):231-6
86. Von Lubitz DK, Lin RC, Paul IA, et al. Postischemic administration of adenosine amine congener (ADAC): analysis of recovery in gerbils. Eur J Pharmacol 1996;316(2-3):171-9
87. Knutsen LJ, Lau J, Petersen H, et al. N-substituted adenosines as novel neuroprotective A1; agonists with diminished hypotensive effects. J Med Chem 1999;42(18):3463-77
88. Jacobson KA, Von Lubitz DK, Daly JW, Fredholm BB. Adenosine receptor ligands: differences with acute versus chronic treatment. Trends Pharmacol Sci 1996;17(3):108-13
89. Coelho JE, Rebola N, Fragata I, et al. Hypoxia-induced desensitization and internalization of adenosine A1 receptors in the rat hippocampus. Neuroscience 2006;138(4):1195-203
90. NCT00182312. Caffeine for apnea of prematurity (CAP). Available from: http://clinicaltrials.gov/ct2/show/NCT00182312
91. Schmidt B, Roberts RS, Davis P, et al. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 2007;357(19):1893-902
92. Rezvani ME, Mirnajafi-Zadeh J, Fathollahi Y, Palizvan MR. Anticonvulsant effect of A1 but not A2A adenosine receptors of piriform cortex in amygdala-kindled rats. Can J Physiol Pharmacol 2007;85(6):606-12
93. Schindler CW, Karcz-Kubicha M, Thorndike EB, et al. Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A1 and A2A subtype receptor agonists. Br J Pharmacol 2005;144(5):642-50
94. Lee HT, Emala CW. Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A1; and A3; receptors. Am J Physiol Renal Physiol 2000;278(3):F380-7
95. Lee HT, Xu H, Nasr SH, et al. A1 adenosine receptor knockout mice exhibit increased renal injury following ischemia and reperfusion. Am J Physiol Renal Physiol 2004;286(2):F298-306
96. Vallon V, Mühlbauer B, Osswald H. Adenosine and kidney function. Physiol Rev 2006;86(3):901-40
97. Joo JD, Kim M, Horst P, et al. Acute and delayed renal protection against renal ischemia and reperfusion injury with Al adenosine receptors. Am J Physiol Renal Physiol 2007;293(6):F1847-57
98. Vannucci SJ, Klim CM, Martin LF, Lanoue KF. Al-adenosine receptor-mediated inhibition of adipocyte adenylate cyclase and lipolysis in Zucker rats. Am J Physiol Endocrinol Metab 1989;257:E871-8
99. Dong Q Ginsberg HN, Erlanger BF. Overexpression of the Al adenosine receptor in adipose tissue protects mice from obesity-related insulin resistance. Diabetes Obes Metab 2001;3(5):360-6
100. Boden G. Pathogenesis of type 2 diabetes. Insulin resistance. Endocrinol Metab Clin North Am 2001;30(4):801-15
101. Qu X, Cooney G, Donnelly R. Short-term metabolic and haemodynamic effects of GR79236 in normal and fructose-fed rats. Eur J Pharmacol 1997;338(3):269-76
102. Dhalla AK, Wong MY, Voshol PJ, et al. Al adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents. Am J Physiol Endocrinol Metab 2007;292(5):El358-63
103. Wilson CN, Borron P. Methods and compositions for producing antigenic responses. US20050075308; 2005
104. Wilson CN, Batra VK. Lipopolysaccharide binds to and activates Al adenosine receptors on human pulmonary artery endothelial cells. J Endotoxin Res 2002;8:263-71
105. Mayne M, Shepel PN, Jiang Y, et al. Dysregulation of adenosine Al receptor-mediated cytokine expression in peripheral blood mononuclear cells from multiple sclerosis patients. Ann Neurol 1999;45:633-9
106. Johnston JB, Silva C, Gonzalez G, et al. Diminished adenosinc Al receptor expression on macrophages in brain and blood of patients with multiple sclerosis. Ann Neurol 2001;49(5):650-8
107. Welch WJ. Adenosine type 1 receptor antagonists in fluid retaining disorders. Expert Opin Investig Drugs 2002;11(11):1553-62
108. Greenberg B, Thomas I, Banish D, et al. Effects of multiple oral doses of an Al adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study. J Am Coll Cardiol 2007;50(7):600-6
109. NCT00354458. A study of the selective Al adenosine receptor antagonist KW-3902 for patients hospitalized with acute HF and volume overload to assess treatment effect on congestion and renal function. Available from: http://clinicaltrials.gov/ct2/show/NCT00354458
110. NCT00328692. A study of the selective Al adenosine receptor antagonist KW-3902 for patients hospitalized with acute HF and volume overload to assess treatment effect on congestion and renal function. Available from: http://clinicaltrials.gov/ct2/show/NCT00328692
111. NCT00443690. Placebo-controlled randomized study of KW-3902 for subjects hospitalized with worsening renal function and heart failure requiring IV therapy (REACH UP). Available from: http://clinicaltrials.gov/ct2/ show/NCT00443690
112. Dittrich H, Farmer B. Method of improved diuresis in individuals with impaired renal function. W02007149285; 2007
113. Miracle CM, Rieg T, Blantz RC, et al. Combined effects of carbonic anhydrase inhibitor and adenosine Al receptor antagonist on hemodynamic and tubular function in the kidney. Kidney Blood Press Res 2007;30(6):388-99
114. Dittrich HC, Gupta DK, Hack TC, et al. The effect of KW-3902, an adenosine Al receptor antagonist, on renal function and renal plasma flow in ambulatory patients with heart failure and renal impairment. J Card Fail 2007;13(8):609-17
115. Givertz MM, Massie BM, Fields TK, et al. CKI-201 and CKI-202 Investigators. The effects of KW-3902, an adenosine Al-receptor antagonist, on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J Am Coll Cardiol 2007;50(16):1551-60
116. Cleland JG, Coletta AP, Abdellah AT, et al. Clinical trials update from Heart Rhythm and Heart Failure 2007: CARISMA, PREPARE, DAVID II, SAVE-PACE, PROTECT and AREA-IN-CHF. Eur J Heart Fail 2007;9(8):850-3
117. kalk P, Eggert B, Relle K, et al. The adenosine Al receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure. Br J Pharmacol 2007;151(7):1025-32
118. NCT00160134. Study to evaluate cardiac hemodynamics and safety of SLV320 in subjects with congestive heart failure. Available from: http://clinicaltrials.gov/ct2/show/NCT00160134
119. NCT00568009. Study to evaluate the effect of SLV320 in addition to chronic furosemide treatment on renal function in subjects with congestive heart failure and impaired renal function. Available from: http://clinicaltrials.gov/ct2/show/NCT00568009
120. Otsuki L, Widder K. Combination therapy comprising an adenosine Al receptor antagonist and an aldosterone inhibitor. WO2005105083; 2005
121. Dittrich H, Farmer B. Prolonged improvement of renal function comprising infrequent administration of an AAIRA. WO2007149366; 2007
122. Erley CM, Heyne N, Burgett K, et al. Prevention of radiocontrast-induced nephropathy by adenosine antagonists in rats with chronic nitric oxide deficiency. J Am Soc Nephrol 1997;8:1125-32
123. Yao K, Heyne N, Erley CM, et al. The selective adenosine Al receptor antagonist KW-3902 prevents radiocontrast media-induced nephropathy in rats with chronic nitric oxide deficiency. Eur J Pharmacol 2001;414:99-10
124. Hocher B, Fischer Y. Use of adenosine Al antagonists in radiocontrast media induced nephropathy. US2008027082; 2008
125. Spicuzza L, Di Maria G, Polosa R. Adenosine in the airways: implications and applications. Eur J Pharmacol 2006;533(1-3):77-88
126. Nyce JW, Metzger WJ. DNA antisense therapy for asthma in an animal model. Nature 1997;385(6618):721-5
127. Obiefuna PC, Barra VK, Nadeem A, et al. A novel Al adenosine receptor antagonist, L-97-1, 3-2-(4-aminophenyl)-ethyl-8-benzyl-7-{2-ethyl- (2-hydroxy-ethyl)-amino-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione, reduces allergic responses to house dust mite in an allergic rabbit model of asthma. J Pharmacol Exp Ther 2005;315(l):329-36
128. Nadeem A, Obiefuna PC, Wilson CN, Mustafa SJ. Adenosine Al receptor antagonist versus montelukast on airway reactivity and inflammation. Eur J Pharmacol 2006;551(1-3):116-24
129. Wilson CN, Partridge J. Compositions and methods for treating respiratory disorders. WO2007103970; 2007
130. Evans BAJ, Ham J. The role of adenosine in bone: an emerging concept. Immunol Endocrine Metab Agents Med Chem 2007;7(4):322-7
131. Cronstein B, Kara Firas M. Methods and compositions for treating disorders associated with increased bone turnover and osteopenia. WO2007095161; 2007
132. Neely CF, Jin J, Keith IM. Al-adenosine receptor antagonists block endotoxin-induced lung injury. Am J Physiol 1997;272:L353-61
133. Wilson CN, Batra V. Lipopolysaccharide binds to and activates Al adenosine receptors on human pulmonary artery endothelial cells. J Endotoxin Res 2002;8:263-71
134. Wilson CN. Methods and pharmaceutical compositions for treating sepsis. US2006276378; 2006
135. Back SA, Craig A, Luo NL, et al. Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury. Ann Neurol 2006;60(6):696-705
136. Magata S, Taniguchi M, Suzuki T. et al. The effect of antagonism of adenosine Al receptor against ischemia and reperfusion injury of the liver. J Surg Res 2007;139(l):7-14
137. Lee HT, Emala CW. Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of Al; and A3; receptors. Am J Physiol Renal Physiol 2000;278(3):F380-7
138. Brown RA, Spina D, Page CP. Adenosine receptors and asthma. Br J Pharmacol 2008;153(Suppi 1):S446-56
139. Maemoto T. Tada M, Mihara T, et al. Pharmacological characterization of FR194921, a new potent, selective, and orally active antagonist for central adenosine Al receptors. J Pharmacol Sci 2004;96(l):42-52
140. Available from: www.clinicaltrials.gov