Recent progress in the development of Adenosine receptor ligands antiinflammatory drugs

Current Topics in Medicinal Chemistry

Volumn 6, Issue 13, 2006, Pages 1375-1399

  Akkari, Rhalid ^a   Burbiel, Joachim C ^a   Hockemeyer, Jörg ^a   Müller, Christa E ^a  

^a UNIVERSITY OF BONN   (Germany)

Author keywords

Asthma; Inflammation; MRE 0094; Pyrazine derivatives; Pyridazinone derivatives; Xanthine antagonist

Indexed keywords

(6 AMINO 9 ETHYL 8 PYRAZOLYLPURIN 2 YL)BENZYLAMINE; 2 ALKOXY(3' DEOXY)ADENOSINE DERIVATIVE; 2 [4 (2 CARBOXYETHYL)PHENETHYLAMINO]ADENOSINE 5' (N ETHYLCARBOXAMIDE); 5 (2 PHENYL 1 BENZOFURAN 3 YL) 2(1H) PYRIDONE; 5 (5 AMINO 6 BROMO 3 PHENYL 2 PYRAZINYL) 1 ISOPROPYL 2(1H) PYRIDONE; 5 (5 AMINO 6 BROMO 3 PHENYL 2 PYRAZINYL) 3 BROMO 1 ISOPROPYL 2(1H) PYRIDONE; 5 (5 METHOXY 2 PHENYL 1 BENZOFURAN 3 YL) 2(1H) PYRIDONE; 5' ALKYNYLADENOSINE DERIVATIVE; 6 (6 HYDROXY 2 PHENYL 1 BENZOFURAN 3 YL) 2 ISOPROPYL 3(2H) PYRIDAZINONE; ADENOSINE; ADENOSINE 5' (N ETHYLCARBOXAMIDE); ADENOSINE A1 RECEPTOR; ADENOSINE A1 RECEPTOR AGONIST; ADENOSINE A1 RECEPTOR ANTAGONIST; ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR AGONIST; ADENOSINE A2A RECEPTOR ANTAGONIST; ADENOSINE A2B RECEPTOR; ADENOSINE A3 RECEPTOR; ADENOSINE A3 RECEPTOR AGONIST; ADENOSINE A3 RECEPTOR ANTAGONIST; ADENOSINE DEAMINASE INHIBITOR; ADENOSINE KINASE INHIBITOR; ADENOSINE RECEPTOR; ANTIINFLAMMATORY AGENT; G PROTEIN COUPLED RECEPTOR; LIGAND; LIGNAN DERIVATIVE; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALLOSTERISM; ANTIINFLAMMATORY ACTIVITY; ANTINOCICEPTION; ARTHRITIS; ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; DEPRESSION; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DYSKINESIA; DYSTONIA; HUMAN; HUNTINGTON CHOREA; INFLAMMATORY DISEASE; NEUROPATHIC PAIN; NONHUMAN; PAIN; PARKINSON DISEASE; PROTEIN FAMILY; PSYCHOSIS; REVIEW; SEPSIS; SIGNAL TRANSDUCTION;

EID: 33746611084     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/15680266106061375     Document Type: Review

References (160)

1. 2A Receptors in Downregulation of Inflammation and Immunity in the Pathogenesis of Infectious Diseases. Microbes Infect 2003, 5, 515-526.
2. 2A Receptor Agonists as Antiinflammatory Agents. Curr. Opin. Invest. Drugs 2003, 4, 1313-1319
3. Livingston, M.; Heaney, L. G.; Ennis, M. Adenosine, Inflammation and Asthma - a Review. Inflammation Rev. 2004, 53, 171-178.
4. Fredholm, B. B.; IJzerman, A. P.; Jacobson, K. A.; Klotz, K. N.; Linden, J. International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors. Pharmacol. Rev. 2001, 53, 527-552.
5. Yan, L., Burbiel, J. C.; Maass, A.; Müller, C. E. Adenosine Receptor Agonists: from Basic Medicinal Chemistry to Clinical Development. Expert Opin. Emerg. Drugs 2003, 8, 537-576.
6. Zimmermann, H. Biochemistry, Localization and Functional Roles of Ecto-Nucleotidases in the Nervous System. Prog. Neurobiol. 1996, 49, 589-618.
7. Müller, C.E.; Scior, T. Adenosine receptors and their modulators. Pharm. Acta Helv. 1993, 68, 77-111.
8. Noji, T.; Karasawa, A.; Kusaka, H. Adenosine Uptake Inhibitors. Eur. J. Pharmacol. 2004, 495, 1-16.
9. Liu, N. J.; Salter, M. W. Purines and Pain Mechanisms: Recent Developments. Curr. Opin. Invest. Drugs 2005, 6, 65-75.
10. 1 Antagonism in Asthma: Better than Coffee? J. Clin. Invest. 2005, 115, 13-16.
11. Nyce, J. W.; Metzger, W. J. DNA Antisense Therapy for Asthma in an Animal Model. Nature 1997, 385, 721-725.
12. Bayer AG. Substituted 2-Thio-3,5-Dicyano-4-Aryl-6-Amino-pyridines and the Use Thereof as Adenosine Receptor Ligands. WO 0125210, 2001.
13. Bayer AG. Preparation of 2-Heteroarylmethylthio-3,5-Dicyano-4-Phenyl-6-Aminopyridines as Adenosine Receptor Selective Ligands. WO 03008383, 2003.
14. Beukers, M. G.; Chang, L. C. W.; von Frijtag, J. K.; Spanjersberg, R. F.; Brussee, J.; Ijzerman, A. P. New, Non-Adenosine, High-Potency Agonists for the Human Adenosine A2B Receptor with an Improved Selectivity Profile Compared to the Reference Agonist N-Ethylcarboxamidoadenosine. J. Med. Chem. 2004, 47, 3707-3709.
15. Jacobson, M. A. Adenosine Receptor Agonists. Expert Opin. Ther Patent 2002, 12, 489-501.
16. 1 Receptor Ligands. Curr. Top. Med. Cheyn. 2003, 3, 355-67.
17. 1 Receptor Agonists. WO 04026890, 2004.
18. Poulsen, S. A.; Quinn, R. J. Adenosine Receptors: New Opportunities for Future Drugs. Bioorg. Med. Chem. 1998, 6, 619-641.
19. 1 Agonists as Potential Analgesics. Med. Chem. Res. 2004, 13, 88-98.
20. 1 Adenosine Receptor. J. Med. Chem. 2000, 43, 250-260.
21. 3 Receptors. J. Med. Chem. 2001, 44, 2966-2975.
22. 1 Adenosine Receptors. J. Nat. Prod. 2002, 65, 1479-1485.
23. Kehraus, S.; Gorzalka, S.; Hallmen, C.; Iqbal, J.; Müller, C. E.; Wright, A. D.; Wiese, M.; König, G. M. Novel Amino Acid Derived Natural Products from the Ascidian Atriolum Robustum: Identification and Pharmacological Characterization of a Unique Adenosine Derivative. J. Med. Chem. 2004, 47, 2243-2255.
24. 1 Receptor Ligand Isolated from Salvia Miltiorrhiza, Bunge (Danshen). Tetrahedron Lett. 1991, 32, 2061-2064.
25. van Rhee, A.M.; Siddiqi, S.M.; Melman, N.; Shi, D.; Padgett, W.L.; Daly, J.W.; Jacobson, K.A. Tetrahydrobenzothiophenone Derivatives as a Novel Class of Adenosine Receptor Antagonists. J. Med. Chem. 1996, 39, 398-406.
26. 2 Adenosine Receptor Antagonists. Pure Appl. Chem. 2001, 73, 1411-1420.
27. 1 Adenosine Receptor Antagonists. WO 05009343, 2005.
28. 1 Adenosine Receptor Antagonists. WO 05009445, 2005.
29. Fujisawa Pharmaceutical Co.,Ltd. Preparation of Pyridones and Pyridazinones as Adenosine Antagonists and Pharmaceutical Use Thereof. WO 04022540, 2004.
30. 2A Receptor Antagonists and their Pharmaceutical Compositions. WO 05040151, 2005.
31. Fujisawa Pharmaceutical Co.,Ltd. Preparation of Condensed Furan Derivatives as Adenosine Antagonists for Treatment of CNS Disorders. WO 04089939, 2004.
32. Ohta, A.; Sitkovsky, M. Role of G-Protein-Coupled Adenosine Receptors in Down Regulation of Inflammation and Protection of Tissue Damage. Nature 2001, 414, 916-920.
33. 2A Adenosine Receptor as a Physiological Immunosuppressor and to Engineer Inflammation In Vivo. Biochem. Pharmacol. 2003, 65, 493-501.
34. 2A Adenosine Receptor Agonists. US 5,877,180, 1999.
35. Linden, J.M.; Sullivan, G.W.; Scheld W.M. Method Compositions for Treating the Inflammatory Response. US 6,514,949, 2003.
36. Cambridge Biotechnology Ltd.; Richardson, P. Use of Adenosine Receptor Agonists in Therapy. WO 04078184, 2004.
37. 2A Receptor Agonist, on Allergic Airways Inflammation in the rat. Eur. J. Pharmacol. 2002, 438, 183-188.
38. 2A-Receptor Agonists and Tiotropium or a Derivative Thereof for Treating Obstructive Airways and Other Inflammatory Disease. WO 02094273, 2002.
39. Mazar, J.; Rogachev, B.; Shaked, G.; Nadav, Y.; Czeiger, D.; Chaimovitz, C.; Zlonik, M.; Mukmenev, I.; Byk, G.; Douvdevani, A. Involvement of Adenosine in the Anti-Inflammatory Action of Ketamine. Anesthesioloey 2005, 102, 1174-1181.
40. Belardinelli, L.; Linden, J.; Berne, R.M. The Cardial Effects of Adenosine. Prog. Cardiovas. Dis. 1989, 32, 73-97.
41. 2A Adenosine Receptor Domain Specifically Responsible for Mediating Short-Term Desensitization. Biochemistry 1997, 36, 832-838.
42. 2A Receptor Agonists. Curr. Top. Med. Chem. 2003, 3, 387-401.
43. Klotz, K.; Hessling, J.; Hegler J.; Owman, C.; Kull, B.; Fredholm, B.; Lohse, M. Comparative Pharmacology of Human Adenosine Receptor Subtypes - Characterisation of Stably Transfected Receptors in CHO Cells. Nauny-Schmiedeberg's Arch. Pharmacol. 1998, 357, 1-9.
44. 2A Adenosine Receptor and its Agonists. Chem. Biol. 2005, 12, 237-247.
45. 2 (G Alpha s-linked) Receptors. J. Exp. Med. 1997, 186, 1615-1620.
46. Cronstein, B. Adenosine Receptors and Wound Healing. Scientific WorldJournal 2004, 4, 1-8.
47. 2 Adenosine Receptor. J. Med. Chem. 1991, 34, 1340-1344.
48. Bizbiotech Co., Ltd. Compounds, Compositions and Methods. WO 05030121, 2005.
49. 2A Receptor Agonists. Br. J. Pharmacol. 2001, 132, 1017-1026.
50. 2A Analogue Improves Neurologic Outcome after Spinal Cord Trauma in the Rabbit. J. Trauma 2002, 53, 225-229.
51. 2A Receptor Activation Decreases Reperfusion Injury Associated with High-Flow Reperfusion. J. Thorac. Cardiovasc. Surg. 2002, 124, 973-978.
52. 2A Adenosine Receptor Activation Reduces Skin Pressure Ulcer Formation and Inflammation. Am. J. Physiol. Heart Circ. Physiol. 2001, 281, 67-74.
53. 2A Adenosine Receptor Agonist to Reduce Inflammatory Response in Transplanted Tissue. US 2005/182018, 2005.
54. 2A Agonist Activity and Compositions Thereof. WO 03029264, 2003.
55. 2A Receptor. Bioorg. Med. Chem. 2003, 11, 2183-2192.
56. Glaxo Group Ltd.; Cox, B.; Keeling, S.; Allen, D.; Redgrave, A.; Barker, M.; Hobbs, H.; Roper, T.; Geden, J. 2-(Purin-9-yl)-Tetrahydrofuran-3,4-Diol Derivatives. WO 9828319, 1998.
57. Glaxo Group Ltd.; Johnson, P. Pharmaceutical Aerosol Formulation. WO 02072067, 2002.
58. 2A Adenosine Receptor. J. Med. Chem. 2004, 47, 4041-4053.
59. 2A Receptor Antagonists. Curr. Opin. Drug Discovery Dev. 2005, 8, 458-468.
60. Bilkei-Gorzo, A.; Abo-Salem, O. M.; Hayallah, A. M.; Michel, K.; Müller, C. E.; Zimmer, A. Adenosine Receptor Subtypes in Inflammation and Hyperalgesia. submitted.
61. 2A Receptor Antagonists as Neuroprotective Agents. Curr. Med. Chem. - Centr. Nerv. Sys. Agents 2004, 4, 35-45.
62. Pierri, M.; Vaudano, E.; Sager, T.; Englund, U. KW-6002 Protects from MPTP Induced Dopaminergic Toxicity in the Mouse. Neuropharmacology 2005, 48, 517-524.
63. 2A Receptor Binding and Phosphodiesterase Inhibiting Activity for the Treatment of Neurodegenerative Disorders and Inflammation Related Diseases. WO 03088963, 2003.
64. 2B Receptor Activation Selectively Stimulates cAMP Formation and Inhibition of TNFα Release in THP-1 Cells. Drug Dev. Res. 1998, 44, 41-47.
65. Xaus, J.; Valledor, A. F.; Cardo, M.; Marques, L.; Beleta, J.; Palacios, J. M.; Celada, A. Adenosine Inhibits Macrophage Colony-Stimulating Factor-Dependent Proliferation of Macrophages Through the Induction of p27kip-1 Expression. J. Immunol. 1999, 163, 4140-4149.
66. Fozard, J. R.; McCarthy, C. Adenosine Receptor Ligands as Potential Therapeutics in Asthma. Curr. Opin. Invest. Drugs 2002, 3, 69-77.
67. 2B Receptors Evoke Interleukin-8 Secretion in Human Mast Cells: an Enprofylline-Sensitive Mechanism with Implication for Asthma. J. Clin. Invest. 1995, 96, 1979-1986.
68. Wolber, C.; Fozard, J. R. The Receptor Mechanism Mediating the Contractile Response to Adenosine on Lung Parenchymal Strips from Actively Sensitized, Allergen-Challenged Brown Norwegian Rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 2005, 371, 158-168.
69. 2B Receptor as a Novel Therapeutic Target in Asthma. Br. J. Pharmacology 2005, 145, 1009-1015.
70. 2B Adenosine Receptor Antagonists. J. Pharmacol. Exp. Ther. 2004, 308, 358-366.
71. 2B Adenosine Receptors. Drug Dev. Res. 1999, 47, 178-188.
72. 2B Adenosine Receptor Antagonist for the Potential Treatment of Asthma. Bioorg. Med. Chem. Lett. 2005, 15, 609-612.
73. Müller, C. E.; Shi, D.; Manning, M.; Daly, J. W. Synthesis of Paraxanthine Analogs (1,7-Disubstituted Xanthines) and Other Xanthines Unsubstituted at the 3-Position: Structure-Activity Relationship at Adenosine Receptors. J. Med. Chem. 1993, 36, 3341-3349.
74. 2B-Selective Adenosine Receptor Antagonists. J. Med. Chem. 2002, 45, 1500-1510.
75. 2B Adenosine Receptor Antagonists. J. Med. Chem. 2004, 47, 1434-1447.
76. 2B Adenosine Receptor Antagonists. WO 05042534, 2005.
77. Stefanachi, A.; Leonetti, F.; Cappa, A.; Carotti, A. Fast and Highly Efficient One-Pot Synthesis of 9-Deazaxanthines. Tetrahedron Lett. 2003, 44, 2121-2123.
78. 2-Adenosine Receptor Antagonists. J. Med. Chem. 1994, 37, 1526-1534.
79. 2B. Eur. J. Med. Chem. 2004, 39, 879-887.
80. CV Therapeutics Inc.; Kalla, R.; Perry, T.; Elzein, E.; Varkhedkar, V.; Li, X.; Ibrahin, P.; Palle, V.; Xiao, D.; Zablocki, J.; A2B Adenosine Receptor Antagonists. US 6825349, 2004.
81. Almirall Prodesfarma S. A.; Vidal, B.; Esteve, C. New 4-(Pyrrolopyrimidin-6-yl)benzenesulphonamide Derivatives. WO 03082873, 2003.
82. 2B Receptors. Biochem. Pharmacol. 2004, 68, 305-312.
83. Adenosine Therapeutics. Substituted 8-Heteroaryl Xanthines. WO 05021548, 2005.
84. 2B Adenosine Receptor Antagonists. WO 05040155, 2005.
85. 2B Antagonists. WO 05070926, 2005.
86. 2B Selective Antagonist Compounds, their Synthesis and Use. WO 03053366, 2003.
87. 2B Adenosine Receptors. Curr. Top. Med. Chem. 2003, 3, 427-443.
88. 3 Adenosine Receptors. Mini-Rev. Med. Chem. 2001, 1, 417-427 and references therein
89. 3 Receptor is the Unique Adenosine Receptor which Facilitates Release of Allergic Mediators in Mast Cells. J. Biol. Chem. 1993, 268, 16887-16890.
90. 3 Adenosine Receptors. Biochem. Pharmacol. 2003, 65, 1675-1684
91. Jacobson, K.; Knutsen, L. P1 and P2 Purine and Pyrimidines Receptors. In: Purinergic and Pyrimidinergic Signalling. Abbracchio M. P., Williams M et al. (Eds) Handbook of Experimental Pharmacology, Springer-Verlag, Berlin 2001, 129-175.
92. Jacobson, K.; Suzuki, F. Recent Developments in Selective Agonists and Antagonists Acting at Purine and Pyrimidine Receptors. Drug Dev. Res. 1996, 39, 289-300.
93. 3 Adenosine Receptors: Protective vs. Damaging Effects Identified Using Novel Agonists and Antagonists. Drug. Dev. Res. 1998, 45, 113-124
94. 3 Adenosine Receptor Ligands: History and Perspectives. Med. Res. Rev. 2000, 20, 103-128.
95. 3 Adenosine Receptor Signalling Contributes to Airway Inflammation and Mucus Production in Adenosine Deaminase-Defficient Mice. J. Immunol. 2004, 173, 1380-1390.
96. 3 Receptor Ligands. Curr. Top. Med. Chem. 2003, 3, 445-462.
97. 3 Adenosine Receptors. J. Med. Chem. 1994, 37, 3614-3621.
98. 3 Adenosine and P2Y Nucleotide Receptors and their Ligands. Drug. Dev. Res. 2003, 58, 330-339.
99. 3 Adenosine Receptor. Biochem. Pharmacol. 2002, 63, 157-161.
100. 3 AR Agonists for the Treatment of Inflammatory Arthritis. WO 04045627, 2004.
101. Jeong, L.; Jacobson, K.; Moon, H.; Kim, H. Purine Nucleosides. WO 04038006, 2004.
102. 3 Receptor Agonists. WO 04022573, 2004.
103. 3 Receptors in Mast Cells. Trends Pharmacol. Sci. 1994, 15, 13-14.
104. Fan, M.; Qin, W.; Mustafa, S. J. Characterization of Adenosine Receptor(s) Involved in Adenosine-Induced Bronchoconstriction in an Allergic Mouse Model. Am. J. Phys.-Lung 2003, 284, 1012-1019.
105. 3 Adenosine Receptor Antagonists. US 6387913, 2002.
106. Press, N.J.; Taylor, R Aminothiazoles and their Use as Adenosine Receptor Antagonists. WO 0242298, 2002.
107. 3 Receptor Antagonists. Curr. Top. Med. Chem. 2004, 4, 863-870.
108. Trifelieff, A.; Keller, T.; Press, N. J.; Howe, T.; Gedeck, P.; Beer, D.; Walker, C. CGH2466, a Combined Adenosine Receptor Antagonist, p38 Mitogen-Activated Protein Kinase and Phosphodiesterase Type 4 Inhibitor with Potent In Vivo and In Vitro Anti-Inflammatory Activities. Br. J. Pharmacol. 2005, 144, 1002-1010.
109. 3 Receptor Antagonist with Therapeutic Potential. Med. Chem. Lett. 2005, 15, 3081-3085.
110. Matuszczak, B; Müller, C. E.; Beer, M. Pyrazolyl-Substituted Triazoloquinoxalines. WO 03053973, 2003.
111. Aranyi, P.; Balazs, L.; Batori, S.; Bence, J.; Nagy, L.; Boer, K.; Hajdu, F; Kapui, Z. Triazolo-Quinoline Derivatives Useful as Adenosine Receptor Ligands. WO 03053968, 2004.
112. 3 Receptor Ligands. WO 04046146, 2004.
113. 3 Ligands. WO 05009969, 2005.
114. 3 Adenosine Receptor Antagonists. J. Med. Chem. 1999, 42, 4473-4478.
115. Baraldi, P.; Cacciari, B.; Borea, P. Pyrazolo-Triazolo-Pyrimidine Derivatives as Adenosine Receptor Antagonists: a Possible Template for Adenosine Receptor Subtypes? Curr. Pharm. Des. 2002, 8, 2299-2332.
116. 3 Adenosine Receptor Antagonists. Drug Dev. Res. 2003, 58, 315-329.
117. 3 Adenosine Receptors Antagonists. J. Med. Chem. 2003, 46, 1229-1241.
118. Baraldi, P; Borea, P.; Butler, G. Pharmaceutically Active Compounds Having a Tricyclic Pyrazolotriazolopyrimidine Ring Structure and Methods of Use. WO 03101455, 2003.
119. 2 Adenosine Receptor Antagonists. J. Med. Chem. 2000, 43, 4636-4646.
120. 1 Adenosine Receptor Antagonists. J. Med. Chem. 1996, 39, 2482-2491.
121. 1 Selective Adenosine Receptor antagonists. J. Med. Chem. 1990, 33, 2822-2828.
122. Castelhano, A.; McKibben, B.; Witter, D. Compounds Specific to Adenosine A3 Receptors and Uses Thereof. US 2003/0073708, 2003.
123. 3 Receptors and Uses Thereof. WO 03048120, 2003.
124. 3 Receptors. US 2004/0038972, 2004.
125. 1 Receptor Binding by 2-Amino-3-Benzoylthiophenes. Mol. Pharmacol. 1990, 38, 950-958.
126. Gao, Z.-G.; Kim, S. K.; IJzerman A. P.; Jacobson K. A.; Allosteric Modulation of the Adenosine Family of Receptors. Mini-Rev. Med. Chem. 2005, 5, 545-553
127. King Pharmaceuticals, Allosteric Adenosine Receptor Modulation. EP1401441A2, 2004.
128. Baraldi P.G. Allosteric Adenosine Receptor Modulators. US 2004/0077630 A1, 2004.
129. 1 Receptor Eur. J. Med. Chem. 2004, 39, 855-865.
130. Baraldi, P. G.; Romagnoli, R.; Pavani, M. G.; Nunez, Mdel, C.; Tabrizi, M. A.; Shryock, J. C., Leung, E.; Moorman, A. R.; Uluoglu, C.; Ianotta, V.; Merighi, S.; Borea, P. A. Synthesis and Biological Effects of Novel 2-Amino-3-naphthoylthiphenes as Allosteric Enhancers of the A1 Adenosine Receptor. J. Med. Chem. 2003, 46, 794-809.
131. 1 Adenosine Agonist Binding: New 3,4- and 5-Modifications J. Med. Chem. 2003, 46, 1870-1877.
132. 1 Adenosine Receptors. Bioorg. Med. Chem. Lett. 2002, 12, 1563-1566.
133. Li, X.; Conklin, D.; Pan, H.-L.; Eisenach, J. C. Allosteric Adenosine Receptor Modulation Reduces Hypersensitivity Following Peripheral Inflammation by a Central Mechanism. J. Pharmacol. Exp. Therap. 2003, 305, 950-955.
134. Kowaluk, E. A.; Bhagwat, S. S.; Jarvis, M. F. Adenosine Kinase Inhibitors. Curr. Pharm. Des. 1998, 4, 403-416.
135. Cronstein, B. N.; Naime, D.; Firestein, G. The Anti-Inflammatory Effects of an Adenosine Kinase Inhibitor are Mediated by Adenosine. ArthritisRheum. 1995, 38, 1040-1045.
136. Gomtsyan, A.; Lee, C. H. Nonnucleoside Inhibitors of Adenosine Kinase. Curr. Pharm. Des. 2004, 10, 1093-1103.
137. Kowaluk, E. A.; Jarvis, M. F. Therapeutic Potential of Adenosine Kinase Inhibitors. Exp. Opin. Invest. Drugs 2000, 9, 551-564.
138. McGaraughty, S.; Chu, K. L.; Wismer, C. T.; Mukusa, J.; Zhu, C. Z.; Cowart, M.; Kowaluk, E. A.; Jarvis, M. F. Effects of A-134974, a Novel Adenosine Kinase Inhibitor, on Carrageenan-Induced Inflammatory Hyperalgesia and Locomotor Activity in Rats: Evaluation of the Sites of Action. J. Pharmacol. Exp. Ther. 2001, 296, 501-509.
139. Boyer, S. H.; Ugarkar, B. G.; Solbach, J.; Kopcho, J.; Matelich, M. C.; Ollis, K.; Gomez-Galeno, J. E.; Mendonca, R.; Tsuchiya, M.; Nagahisa, A.; Nakane, M.; Wiesner, J. B.; Erion, M. Adenosine Kinase Inhibitors. 5. Synthesis, Enzyme Inhibition, and Analgesic Activity of Diaryl-Erythro-Furanosyltubercidin Analogues. J. Med. Chem. 2005, 48, 6430-6441.
140. Bookser, B. C.; Matelich, M. C.; Ollis, K.; Ugarkar, B. G. Adenosine Kinase Inhibitors. 4. 6,8-Disubstituted Purine Nucleoside Derivatives. Synthesis, Conformation, and Enzyme Inhibition. J. Med. Chem. 2005, 48, 3389-3399.
141. Metabasis Therapeutics Inc. Orally Active Adenosine Kinase Inhibitors. EP 0832092B1, 2004.
142. Metabasis Therapeutics Inc. Water-Soluble Adenosine Kinase Inhibitors. EP0836613B1, 2005.
143. Gensia Sicor Inc. C-4′ Modified Adenosine Kinase Inhibitors. EP0832091B1, 2004.
144. Jarvis, M. F.; Yu, H.; Kohlhaas, K.; Alexander, K.; Lee, C.-H.; Jiang, M.; Bhagwat, S. S.; Williams, M.; Kowaluk, E. ABT-702 (4-Amino-5-3-Bromophenyl)-7-(6-Morpholino-Pyridin-3-y1)Pyrido [2,3-d]Pyrimidine), a Novel Orally Effective Adenosine Kinase Inhibitor with Analgesic and Anti-Inflammatory Properties: I. In vitro Characterization and Acute Antinociceptive Effects in the Mouse. J. Pharmacol. Exp. Ther. 2000, 295, 1156-1164.
145. Suzuki, R.; Stanfa, L. C.; Kowaluk, E. A.; Williams, M.; Jarvis, M. F.; Dickenson, A. H. The Effect of ABT-702, a Novel Adenosine Kinase Inhibitor, on the Responses of Spinal Neurones Following Carrageenan Inflammation and Peripheral Nerve Injury. Br. J. Pharmacol. 2001, 132, 1615-1623.
146. Boyle, D. L.; Kowaluk, E. A.; Jarvis, M. F.; Lee, C.-H.; Bhagwat, S. S.; Williams, M.; Firestein, G. S.; Anti-Inflammatory Effects of ABT-702, a Novel Non-Nucleoside Adenosine Kinase Inhibitor, in Rat Adjuvant Arthritis. J. Pharmacol. Exp. Ther. 2000, 296, 495-500.
147. Perner, R. J.; Lee, C. H.; Jiang, M.; Gu, Y. G.; Didomenico, S.; Bayburt, E. K.; Alexander, K. M.; Kohlhaas, K. L.; Jarvis, M. F.; Kowaluk, E. L.; Bhagwat, S. S. Synthesis and Biological Evaluation of 6,7-Disubstituted 4-Aminopyrido[2,3-d]Pyrimidines as Adenosine Kinase Inhibitors. Bioorg. Med. Chem. Lett. 2005, 15, 2803-2807.
148. Gomtsyan, A.; Didomenico, S.; Lee, C.-H.; Matulenko, M. A.; Kim, K.; Kowaluk, E. A.; Wismer, C. T.; Mikusa, J.; Yu, H.; Kohlhaas, K.; Jarvis, M. F.; Bhagwat, S. S. Design, Synthesis, and Structure-Activity Relationship of 6-Alkynylpyrimidines as Potent Adenosine Kinase Inhibitors. J. Med. Chem. 2002, 45, 3639-3648.
149. Gomtsyan, A.; Didomenico, S.; Lee, C. H.; Stewart, A. O.; Bhagwat, S. S.; Kowaluk, E. A.; Jarvis, M. F. Synthesis and Biological Evaluation of Pteridine and Pyrazolopyrimidine Based Adenosine Kinase Inhibitors. Bioorg. Med. Chem. Lett. 2004, 14, 4165-4168.
150. Bauser, M.; Delapierre, G.; Hauswald, M.; Flessner, T.; D'Urso, D.; Hermann, A.; Beyreuther, B.; De Vry, J.; Spreiyer, P.; Reissmüller, E.; Meier, H. Discovery and Optimization of 2-Aryl Oxazolopyrimidines as Adenosine Kinase Inhibitors Using Liquid Phase Parallel Synthesis. Bioorg. Med. Chem. Lett. 2004, 14, 1997-2000.
151. Hashikawa, T.; Hooker, S. W.; Maj, J. G.; Knott-Craig, C. J.; Takedachi, M.; Murakami, S.; Thompson, L. F. J. Regulation of Adenosine Receptor Engagement by Ecto-Adenosine Deaminase. FASEB J. 2004, 18, 131-133.
152. Blackburn, M. R.; Kellems, R. E.; Adenosine Deaminase Deficiency: Metabolic Basis of Immune Deficiency and Pulmonary Inflammation. Adv. Immunol. 2005, 86, 1-41.
153. Terasaka, T.; Non-Nucleoside Adenosine Deaminase Inhibitors 2000-2004. Exp. Opin. Ther. Patents 2005, 15, 817-828.
154. Terasaka, T.; Tsuji, K.; Kato, T.; Nakanishi, I.; Kinoshita, T.; Kato, Y.; Kuno. M.; Inoue, T.; Tanaka, K.; Nakamura, K. Rational Design of Non-Nucleoside, Potent, and Orally Bioavalable Adenosine Deaminase Inhibitors: Predicting Enzyme Conformational Change and Metabolism. J. Med. Chem. 2005, 48, 4750-4753.
155. Da Settimo, F.; Primofiore, G.; La Motta, C.; Taliani, S.; Simorini, F.; Marini, A. M.; Mugnaini, L.; Lavecchia, A.; Novellino, E.; Tuscano, D.; Martini, C. Novel, Highly Potent Adenosine Deaminase Inhibitors Containing the Pyrazolo[3,4-d]Pyrimidine Ring System. Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies. J. Med. Chem. 2005, 48, 5162-5174.
156. Qiu, F.-H.; Wada, K.; Stahl, G. L.; Serhan, C. N. IMP and AMP Deaminase in Reperfusion Injury Down-Regulates Neutrophil Recruitment. Proc. Natl. Acad. Sci. 2000, 97, 4267-4272.
157. Kasibhatla, S. R.; Bookser, B. C.; Xiao, W.; Erion, M. D. AMP Deaminase Inhibitors. 5. Design, Synthesis, and SAR of a Highly Potent Inhibitor Series. J. Med. Chem. 2001, 44, 613-618.
158. Gensia Inc. Novel Inhibitors of Adenosine Monophosphate Deaminase. CA2154577, 2005.
159. Noji, T.; Karasawa, A.; Kusaka, H. Adenosine Uptake Inhibitors. Eur. J. Pharmacol. 2004, 495, 1-16.
160. Buolamwini, J. K. Novel Nucleoside Transport Inhibitors. WO 04060902 A2, 2004.