Feoktistov et al. TIPS 19: 148-152, 1998.* |
Campbell, R.M. et al., “Selective A1-Adenosine Receptor Antagonists Identified Using Yeast Saccharomyces Cerevisae Functional Assays” Bioorg. & Med. Chem. Lett. (1999) 9(16): 2413-2418 (Exhibit 1). |
Zhao, Z. et al., “Bioactivation of 6,7-Dimethyl-2,4-di-1-pyrrolidinyl-7H-pyrrolo[2,3-d]pyrimidine (U-89843) to Reactive Intermediates that Bind Covalently to Macromolecules and Produce Genotoxicity” Chem. Res. Toxicol., (1996) 9: 1230-1239 (Exhibit 2). |
Dhainaut, A. et al., “New Purines and Purine Analogs as Modulators of Multidrug Resistance” J. Med. Chem. (1996) 39: 4099-4108 (Exhibit 3). |
Abbracchio M., et al., (1999) “Brain Adenosine Receptors as Targets for Therapeutic Intervention in Neurodegenerative Diseases”, Ann. NY. Acad. Sci, 890: 79-92 (Exhibit 3). |
Brand A., et al., (2001) “Adenosine A1 and A3 receptors mediate inhibition of synaptic transmission in rat cortical neurons”, Neuropharmacology, 40: 85-95 (Exhibit 4). |
Lee T., et al., (2000) “Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A1 and A3 receptors”, Am. J. Physiol. Renal Physiol., 278: F380-F387 (Exhibit 5). |
Lee T., et al., (1999) “Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A1 and A3 receptors”, 72nd Scientific Sessions of the American Heart Association, Atlanta, GA, p. 197 (Exhibit 6). |
Pichler, H. et al., “Syntheses von 7-unsubstituierten 7h-Pyrrolo[2, 3-d] pyrimidinen”, (1986) Liebigs Ann. Chemie., 9: 1485-1505 (Exhibit 7). |
Williams, E. F. et al., “Nucleoside transport sites in a cultured human retinal cell line established by SV-40 T antigen gene”, (1994) Current Eye Research, 13: 109-118 (Exhibit 8). |
Woods, C. L. and Blazynski, C. (1991) “Characterization of Adenosine A1-receptor Binding Sites in Bovine Retinal Membranes”, Experimental Eye Research, 53: 325-331 (Exhibit 9). |
Nyce, J. W. and Metzger, J.W., (1997) “DNA antisense therapy for asthma in an animal model”, Nature, 385: 721-725 (Exhibit 10). |
Wolff, Manfred E., Burger's Medicinal Chemistry and Drug Discovery, 5th ed., vol. I: Principles and Practice, John Wiley & Sons, 1995, pp. 975-977 (Exhibit 1). |
Banker, G.S. et al., Modern Pharmaceutics, 3rd ed., Marcel Dekker, New York, 1996, p. 596 (Exhibit 2). |
Shan, Daxian et al., J. Pharmaceutical Sci., (1997) 86:765-767 (Exhibit 3). |
Welch, W.J. “Adenosine type 1 receptor antagonists in fluid retaining disorders” Expert Opin. Investig. Drugs (2002), 11(11): 1553-1562 (Exhibit 4). |
Cummings, J. et al., “Antagonism of the Cardiodepressant Effects of Adenosine during Acute Hypoxia” Academic Emergency Medicine (2000), 7(8): 618-624 (Exhibit 5). |
Nishiyama, A., et al., “Adenosine A1 Receptor Antagonist KW-3902 Prevents Hypoxia-Induced Renal Vasoconstriction” J. Pharm. Exp. Ther. (1999), 291: 988-993 (Exhibit 6). |
Szkotak, A.J. et al., “Regulation of K+ current in human airway epithelial cells by exogenous and autocrine adenosine” Am. J. Physiol. Cell Physiol. (2001), 281: C1991-C2002 (Exhibit 7). |
Barett, R.J. et al., “N-0861 selectively antagonizes adenosine A1 receptors in vivo” European J. Pharmacology (1992) 216: 9-16 (Exhibit 10). |
Gao, E. et al., “Adenosine A1 Receptor Antagonist Prolongs Survival in the Hypoxic Rat” J. Cardiovascular Pharm. (2001) 38: 384-394 (Exhibit 11). |
Dooley, M.J. et al., “Theoretical Structure-Activity Studies of Adenosine A1 Ligands: Requirements for Receptor Affinity” Bioorg. Med. Chem. (1996), 4(6): 923-924 (Exhibit 12). |
Seela, F., and Lupke, U., (1977) Mannich-Reaktion am 2-Amino-3,7-dihydropyrrolo [2,3-d] pyrimidin-4-on, dem Chromophor des Ribonucleosids “Q” Chem. Ber (Exhibit 13). |
Chen, Y. L., et al., (1997) “Synthesis and Oral Efficacy of a 4-(Butylethylamino)pyrrolo[2,3-d]pyrimidine: A Centrally Active Corticotropin-Releasing Factor1 Receptor Antagonist”, J. Med. Chem., 40: 1749-1754 (Exhibit 14). |
Bundy, G.L. et al. (1995) “Synthesis of Novel 2,4-Diaminopyrrolo-[2,3-d]pyrimidines with Antioxidant, Neuroprotective, and Antiasthma Activity” J. Med. Chem. 38: 4161-4163 (Exhibit 1). |
Feoktistove, I. et al., (1998) “Adenosine A2B receptors: a novel therapeutic target in asthma?”, TiPS 19: 148-153 (Exhibit 24). |
Muller, C. E. and Stein, B. (1996) “Adenosine Receptor Antagonists: Structures and Potential Therapeutic Applications”, Current Pharmaceutical Design, 2: 501-530 (Exhibit 25). |
Muller, C. E. (1997) “A1-Adenosine Receptor Antagonists”, Exp. Opin. Ther. Patents 7(5): 419-440 (Exhibit 26). |
Muller, C.E., et al., (1997) “Synthesis and Structure-Activity Relationships of 3,7-Dimethyl-1-propargylxanthine Derivatives, A2A-Selective Adenosine Receptor Antagonists”; J. Med. Chem., 40: 4396-4405 (Exhibit 27). |
Iwamura, H. et al., (1996) “Quantitative Aspects of the Receptor Binding of Cytokinin Agonists and Antagonists” J. Med. Chem., 26: 838-844 (Exhibit 44). |
Jorgensen, A. et al. (1985) “Synthesis of 7H-Pyrrolo[2,3-d]pyrimidin-4-amines” Liebigs Ann. Chem., pp. 142-148 (Exhibit 45). |
Kiichiro, K. et al., “Synthesis of pyrazinecarboxylic acid derivs.—(II) derivs. of 3-aminopyrazinecarboxylic acid” (Abstract only) (Exhibit 46). |
Muller, E. C. et al. (1996) “Chiral Pyrrolo[2,3-d]pyrimidine and Pyrimido[4,5-b]indole Derivatives: Structure-Activity Relationships of Potent, Highly Stereoselective A1-Adenosine Receptor Antagonists” J. Med. Chem., 39: 2482-2491 (Exhibit 47). |
Muller, C. E. et al., (1990), “7-Deaza-2-phenyladenines: Structure-Activity Relationships of Potent A1 Selective Adenosine Receptor Antagonists” J. Med. Chem., 33: 2822-2828 (Exhibit 48). |
Venugopalan, B. et al., (1998) “Synthesis of 6,7-Dimethoxypyrimido[4,5-b]-indoles as Potential Antihypertensive Agents” J. Heterocyclic Chem., 25: 1633-1639 (Exhibit 49). |
West, R. A. et al. (1961) “2-Alkyl(aryl)-and 2,7-Dimethyl-4-substituted Aminopyrrolo[2,3-d]pyrimidines” J. Org. Chem., 26: 3809-3812 (Exhibit 50). |
DeNinno, M.P. in Annual Reports in Medicinal Chemistry, vol. 33, (Academis Press: San Diego, 1998), pp. 111-120 (Exhibit 51). |
Hart, H. et al., Organic Chemistry, A Short Course, (Houghton Mifflin: 1995), p. 121 (Exhibit 52). |
Jacobson, K.A., et al., (1998), “Adenosine A3 receptors: novel ligands and paradoxical effects”, TiPS, 19:184-191 (Exhibit 56). |
Jacobson, K.A., et al., (1997) “Pharmacological Characterization of Novel A3 Adenosine Receptor-selective Antagonists”, Neuropharmacology, 36 (9): 1157-1165 (Exhibit 57). |
Mautner, H.G., (1961), “Potential Deoxyribonucleic Acid Crosslinking Agents, 8,8′-Bispurines”, J. Org. Chem. 26(6):1914-1917 (Exhibit 63). |
Kaiser, S.M. and R.J. Quinn (1999) “Adenosine receptors as potential therapeutic targets” Drug Discovery Today 4(12): 542-551 (Exhibit 73). |
Barrett, R.J. (1996) “Realizing the Potential of Adenosine-Receptor-Based Therapeutics” Proc. West. Pharmacol. Soc. 39: 61-66 (Exhibit 74). |
Marx, D. et al. (2001) “Therapy of Bronchial Asthma with Adenosine Receptor Agonists or Antagonists” Drug News Perspect. 14(2): 89-100 (Exhibit 75). |
U.S. patent application Ser. No. 09/454,075, Castelhano et al., filed Dec. 2, 1999. |
U.S. patent application Ser. No. 09/454,074, Castelhano et al., filed Dec. 2, 1999. |
U.S. patent application Ser. No. 09/728,607, Castelhano et al., filed Dec. 1, 2000. |
U.S. patent application Ser. No. 09/728,616, Castelhano et al., filed Dec. 1, 2000. |
U.S. patent application Ser. No. 09/728,229, Castelhano et al., filed Dec. 1, 2000. |
U.S. patent application Ser. No. 10/000,280, Castelhano et al., filed Nov. 30, 2001. |
U.S. patent application Ser. No. 10/006,405, Castelhano et al., filed Nov. 30, 2001. |
U.S. patent application Ser. No. 10/010,092, Castelhano et al., filed Nov. 30, 2001. |
PCT International Preliminary Examination Report for International Application No. PCT/US99/12135 (Exhibit 64). |