Adenosine A2A receptor antagonists and Parkinson's disease

ACS Chemical Neuroscience

Volumn 2, Issue 10, 2011, Pages 555-567

  Shook, Brian C ^a   Jackson, Paul F ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

6 OHDA; A1 receptor antagonist; A2A receptor antagonist; Adenosine; catalepsy; MPTP; Parkinsons disease

Indexed keywords

ADENOSINE A1 RECEPTOR ANTAGONIST; ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR ANTAGONIST;

DRUG ACTIVITY; DRUG MECHANISM; DRUG RESEARCH; DRUG STRUCTURE; DRUG TARGETING; HUMAN; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW;

ADENOSINE A2 RECEPTOR ANTAGONISTS; ANIMALS; ANTIPARKINSON AGENTS; BICYCLO COMPOUNDS, HETEROCYCLIC; HETEROCYCLIC COMPOUNDS; HUMANS; PARKINSON DISEASE; RECEPTOR, ADENOSINE A2A; XANTHINES;

EID: 80054959849     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn2000537     Document Type: Review

References (100)

1. Lozano, A. M., Lang, A. E., Hutchison, W. D., and Dostrovsky, J. O. (1998) New developments in understanding the etiology of Parkinson's disease and in its treatment Curr. Opin. Neurobiol. 8, 783-790 (Pubitemid 28564477)
2. 2 dopamine receptors in rat striatum Mol. Brain Res. 14, 186-195
3. 2receptor mRNA in the human brain Neurosci. Lett. 130, 177-181
4. Olanow, C. W. (1993) MAO-B inhibitors in Parkinson's disease Adv. Neurol. 60, 666-671
5. Gordin, A. and Brooks, D. J. (2007) Clinical pharmacology and therapeutic use of COMT inhibition in Parkinson's disease J. Neurol. 254, IV/37-IV/48
6. Olanow, C. W. and Stocchi, F. (2004) COMT inhibitors in Parkinson's disease. Can they prevent and/or reverse levodopa-induced motor complications? Neurology 62, S72-S81
7. Antonini, A. and Clilia, R. (2009) Behavioural adverse effects of dopaminergic treatments in Parkinson's disease: incidence, neurobiological basis, management and prevention Drug Safety 32, 475-488
8. Hansard, M. J., Smith, L. A., Jackson, M. J., Cheetham, S. C., and Jenner, P. (2002) Dopamine, but not norepinephrine or serotonin reuptake inhibition reverses motor deficits in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-treated primates J. Pharmacol. Exp. Ther. 303, 952-958 (Pubitemid 35424376)
9. Antonini, A., Tolosa, E., Mizuno, Y., Yamamoto, M., and Poewe, W. H. (2009) A reassessment of risks and benefits of dopamine agonists in Parkinson's disease Lancet Neurol. 8, 929-937
10. Yamamoto, M. and Schapira, A. H. V. (2008) Dopamine agonists in Parkinson's disease Expert Rev. Neurother. 8, 671-677 (Pubitemid 351551017)
11. Szaboo, N., Kincses, Z. T., and Veecsei, L. (2011) Novel therapy in Parkinson's disease: adenosine A2A receptor antagonists Expert Opin. Drug Metab. Toxicol. 7, 441-455
12. Salamone, J. D. (2010) Facing dyskinesia in Parkinson's disease: nondopaminergic approaches Drugs Future 35, 567-573
13. Latini, S. and Pedata, F. (2001) Adenosine in the central nervous system: release mechanisms and extracellular concentrations J. Neurochem. 79, 463-484 (Pubitemid 33029920)
14. Dunwiddie, T. V. and Masino, S. A. (2001) The role and regulation of adenosine in the central nervous system Annu. Rev. Neurosci. 24, 31-55 (Pubitemid 32695222)
15. Stiles, G. L. (1992) Adenosine receptors J. Biol. Chem. 267, 6451-6454
16. 2A receptors in rat central nervous system J. Comp. Neurol. 401, 163-186 (Pubitemid 28481960)
17. 2A receptors-where are they? What do they do? Comments Trends Pharmacol. Sci. 19, 46-47
18. 11C]TMSX Synapse 55, 133-136 (Pubitemid 39665672)
19. Svenningsson, P., Hall, H., Sedvall, G., and Fredholm, B. B. (1997) Distribution of adenosine receptors in the postmortem human brain: an extended autoradiographic study Synapse 27, 322-335 (Pubitemid 27479470)
20. Pollack, A. E. and Fink, J. S. (1995) Adenosine antagonists potentiate D2 dopamine dependent activation of Fos in the striatopallidal pathway Neuroscience 68, 721-728
21. Ungerstedt, U. (1968) 6-Hydroxydopamine-induced generation of central monoamine neurons Eur. J. Pharmacol. 5, 107-110
22. Ungerstedt, U. and Arbuthnott, G. W. (1970) Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system Brain Res. 24, 485-493
23. Luthman, J., Fredriksson, A., Sundstroem, E., Jonsson, G., and Archer, T. (1989) Selective lesion of central dopamine or moradenaline neuron systems in the neonatal rat: motor behavior and monoamine alteration at adult stage Behav. Brain Res. 33, 267-277 (Pubitemid 19160683)
24. Bankiewicz, K. S. (1991) MPTP-induced parkinsonism in nonhuman primates Methods Neurosci. 7, 168-182
25. Jakowec, M. W. and Petzinger, G. M. (2004) 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced lesion model of Parkinson's disease, with emphasis on mice and nonhuman primates Comp. Med. 54, 497-513 (Pubitemid 39557443)
26. Campos-Romo, A., Ojeda-Flores, R., Moreno-Briseno, P., and Fernandez-Ruiz, J. (2009) Quantitative evaluation of MPTP-treated nonhuman parkinsonian primates in the hallway task J. Neurosci. Methods 177, 361-368
27. 2A adenosine receptor inactivation in a model of Parkinson's disease J. Neurosci. 21, RC143/1-RC143/6
28. 2A receptor antagonist in MPTP-treated monkeys Neurology 52, 1673-1677 (Pubitemid 29220647)
29. 2A adenosine receptor antagonists on motor dysfunction and neurodegenerative processes Drug Dev. Res. 52, 379-386 (Pubitemid 32401962)
30. 2A receptor blockade in experimental models of Parkinson's disease J. Neurochem. 80, 262-270 (Pubitemid 34809371)
31. 2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys Ann. Neurol. 43, 507-513 (Pubitemid 28231727)
32. 2A receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats Eur. J. Pharmacol. 408, 249-255
33. 2A antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys Exp. Neurol. 162, 321-327 (Pubitemid 30217727)
34. 2A receptor antagonist istradefylline in advanced PD Neurology 61, 297-303 (Pubitemid 36975955)
35. 2A receptor antagonist treatment of Parkinson's disease Neurology 61, 293-296 (Pubitemid 36975954)
36. 1 receptor agonist, on spontaneous and evoked dopamine release in rat neostriatum Neurosci. Lett. 185, 29-32
37. Moore, K. A., Nicoll, R. A., and Schmitz, D. (2003) Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses Proc. Natl. Acad. Sci. U.S.A. 100, 14397-14402 (Pubitemid 37499248)
38. 1 receptors in nerve terminal and synapses of the rat hippocampus Brain Res. 987, 49-58 (Pubitemid 37267886)
39. 1 receptors J. Pharmacol. Sci. 96, 42-52 (Pubitemid 39318777)
40. 1-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure J. Am. Coll. Cardiol. 35, 56-59 (Pubitemid 30061259)
41. Givertz, M. M., Massie, B. M., Fields, T. K., Pearson, L. L., and Dittrich, H. C. (2007) The effects of KW-3902, an adenosine A1-receptor antagonist,on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance J. Am. Coll. Cardiol. 50, 1551-1560 (Pubitemid 47532320)
42. Shah, U. and Hodgson, R. (2010) Recent progress in the discovery of adenosine A2A receptor antagonists for the treatment of Parkinson's disease Curr. Opin. Drug Discovery Dev. 13, 466-480
43. 2A receptor antagonists for Parkinson's disease Expert Opin. Invest. Drugs 18, 1619-1631
44. Baraldi, P. G., Tabrizi, M. A., Gessi, S., and Borea, P. A. (2008) Adenosine Receptor Antagonists: Translating Medicinal Chemistry and Pharmacology into Clinical Utility Chem. Rev. 108, 238-263 (Pubitemid 351176408)
45. 3H]5′-N- ethylcarboxamido adenosine binds to both Ra and Ri adenosine receptors in rat striatum Naunyn-Schmiedeberg's Arch. Pharmacol. 325, 218-225 (Pubitemid 14142499)
46. Cronstein, B. N., Levin, R. I., Belanoff, J., Weissmann, G., and Hirschhorn, R. (1986) Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells J. Clin. Invest. 78, 760-770 (Pubitemid 16024813)
47. Muller, C. E. and Ferre, S. (2007) Blocking striatal adenosine A2A receptors: A new strategy for basal ganglia disorders Recent Pat. CNS Drug Discovery 2, 1-21 (Pubitemid 46729088)
48. Kanda, T., Tashiro, T., Kuwana, Y., and Jenner, P. (1998) Adenosine A2A receptors modify motor function in MPTP-treated common marmosets NeuroReport 9, 2857-2860 (Pubitemid 28435177)
49. Grondin, R., Bedard, P. J., Hadj, T. A., Gregoire, L., Mori, A., and Kase, H. (1999) Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys Neurology 52, 1673-1677 (Pubitemid 29220647)
50. Bara-Jimenez, W., Sherzai, A., Dimitrova, T., Favit, A., Bibbiani, F., Gillespie, M., Morris, M. J., Mouradian, M. M., and Chase, T. N. (2003) Adenosine A2A receptor antagonist treatment of Parkinson's disease Neurology 61, 293-296 (Pubitemid 36975954)
51. Hauser, R. A., Hubble, J. P., and Truong, D. D. (2003) Randomized trial of the adenosine A2A receptor antagonist istradefylline in advanced PD Neurology 61, 297-303 (Pubitemid 36975955)
52. Kyowa Hakko Kogyo Co. Ltd. (2008) Kyowa Hakko receives not approvable letter from FDA for istradefylline (KW-6002). Press Release, February 28.
53. Gatta, F., Del Giudice, M. R., Borioni, A., Borea, P. A., Dionisotti, S., and Ongini, E. (1993) Synthesis of imidazo[1,2- c ]pyrazolo[4,3- e ]pyrimidines, pyrazolo[4,3- e ]1,2,4-triazolo[1,5- c ]pyrimidines and 1,2,4-triazolo[5,1- i ]purines: New potent adenosine A2 receptor antagonists Eur. J. Med. Chem. 28, 569-576 (Pubitemid 23281893)
54. 2A adenosine receptor antagonist Drug Dev. Res. 42, 63-70 (Pubitemid 28188275)
55. Shah, U., Boyle, C. D., Chackalamannil, S., Neustadt, B. R., Lindo, N., Greenlee, W. J., Foster, C., Arik, L., Zhai, Y., Ng, K., Wang, S., Monopoli, A., and Lachowicz, J. E. (2008) Biaryl and heteroaryl derivatives of SCH 58261 as potent and selective adenosine A2A receptor antagonists Bioorg. Med. Chem. Lett. 18, 4199-4203
56. Neustadt, B. R., Hao, J., Lindo, N., Greenlee, W. J., Stamford, A. W., Tulshian, D., Ongini, E., Hunter, J., Monopoli, A., Bertorelli, R., Foster, C., Arik, L., Lachowicz, J., Ng, K., and Feng, K. I. (2007) Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines Bioorg. Med. Chem. Lett. 17, 1376-1380 (Pubitemid 46240836)
57. Hodgson, R. A., Bertorelli, R., Varty, G. B., Lachowicz, J. E., Forlani, A., Fredduzzi, S., Cohen-Williams, M. E., Higgins, G. A., Impagnatiello, F., Nicolussi, E., Parra, L. E., Foster, C., Zhai, Y., Neustadt, B. R., Stamford, A. W., Parker, E. M., Reggiani, A., and Hunter, J. C. (2009) Characterization of the potent and highly selective 2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H- pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] in rodent models of movement disorders and depression J. Pharmacol. Exp. Ther. 330, 294-303
58. Schering-Plough Corp. (2008) Schering-Plough reports preladenant meets primary endpoint in phase II dose-finding trial for Parkinson's disease. Press Release, November 24.
59. Shah, U., Lankin, C. M., Boyle, C. D., Chackalamannil, S., Greenlee, W. J., Neustadt, B. R., Cohen-Williams, M. E., Higgins, G. A., Ng, K., Varty, G. B., Zhang, H., and Lachowicz, J. E. (2008) Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists Bioorg. Med. Chem. Lett. 18, 4204-4209
60. Silverman, L. S., Caldwell, J. P., Greenlee, W. J., Kiselgof, E., Matasi, J. J., Tulshian, D. B., Arik, L., Foster, C., Bertorelli, R., Monopoli, A., and Ongini, E. (2007) 3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A2A antagonists Bioorg. Med. Chem. Lett. 17, 1659-1662 (Pubitemid 46274353)
61. Shook, B. C., Rassnick, S., Hall, D., Rupert, K. C., Heintzelman, G. R., Hansen, K., Chakravarty, D., Bullington, J. L., Scannevin, R. H., Magliaro, B., Westover, L., Carroll, K., Lampron, L., Russell, R., Branum, S., Wells, K., Damon, S., Youells, S., Li, X., Osbourne, M., Demarest, K., Tang, Y., Rhodes, K., and Jackson, P. F. (2010) Methylene amine substituted arylindenopyrimidines as potent adenosine A2A/A1 antagonists Bioorg. Med. Chem. Lett. 20, 2864-2867
62. Shook, B. C., Rassnick, S., Osborne, M. C., Davis, S., Westover, L., Boulet, J., Hall, D., Rupert, K. C., Heintzelman, G. R., Hansen, K., Chakravarty, D., Bullington, J. L., Russell, R., Branum, S., Wells, K. M., Damon, S., Youells, S., Li, X., Beauchamp, D. A., Palmer, D., Reyes, M., Demarest, K., Tang, Y. -T., Rhodes, K., and Jackson, P. F. (2010) In Vivo Characterization of a Dual Adenosine A2A/A1 Receptor Antagonist in Animal Models of Parkinson's Disease J. Med. Chem. 53, 8104-8115
63. Shook, B. C., Rassnick, S., Chakravarty, D., Wallace, N., Ault, M., Crooke, J., Barbay, J. K., Wang, A., Leonard, K., Powell, M. T., Alford, V., Hall, D., Rupert, K. C., Heintzelman, G. R., Hansen, K., Bullington, J. L., Scannevin, R. H., Carroll, K., Lampron, L., Westover, L., Russell, R., Branum, S., Wells, K., Damon, S., Youells, S., Beauchamp, D., Li, X., Rhodes, K., and Jackson, P. F. (2010) Optimization of arylindenopyrimidines as potent adenosine A2A/A1 antagonists Bioorg. Med. Chem. Lett. 20, 2868-2871
64. Harris, J. M., Neustadt, B. R., Zhang, H., Lachowicz, J., Cohen-Williams, M., Varty, G., Hao, J., and Stamford, A. W. (2011) Potent and selective adenosine A2A receptor antagonists: [1,2,4]-triazolo[4,3-c]pyrimidin-3-ones Bioorg. Med. Chem. Lett. 21, 2497-2501
65. Mishra, C. B., Barodia, S. K., Prakash, A., Senthil Kumar, J. B., and Luthra, P. M. (2010) Novel 8-(furan-2-yl)-3-substituted thiazolo [5,4-e][1,2,4] triazolo[1,5-c] pyrimidine-2(3H)-thione derivatives as potential adenosine A2A receptor antagonists Bioorg. Med. Chem. 18, 2491-2500
66. Neustadt, B. R., Liu, H., Hao, J., Greenlee, W. J., Stamford, A. W., Foster, C., Arik, L., Lachowicz, J., Zhang, H., Bertorelli, R., Fredduzzi, S., Varty, G., Cohen-Williams, M., and Ng, K. (2009) Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines Bioorg. Med. Chem. Lett. 19, 967-971
67. Matasi, J. J., Caldwell, J. P., Zhang, H., Fawzi, A., Higgins, G. A., Cohen-Williams, M. E., Varty, G. B., and Tulshian, D. B. (2005) 2-(2-Furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs as adenosine A2A antagonists: The successful reduction of hERG activity Bioorg. Med. Chem. Lett. 15, 3675-3678 (Pubitemid 41038958)
68. Shao, Y., Cole, A. G., Brescia, M.-R., Qin, L.-Y., Duo, J., Stauffer, T. M., Rokosz, L. L., McGuinness, B. F., and Henderson, I. (2009) Synthesis and SAR studies of trisubstituted purinones as potent and selective adenosine A2A receptor antagonists Bioorg. Med. Chem. Lett. 19, 1399-1402
69. Gillespie, R. J., Adams, D. R., Bebbington, D., Benwell, K., Cliffe, I. A., Dawson, C. E., Dourish, C. T., Fletcher, A., Gaur, S., Giles, P. R., Jordan, A. M., Knight, A. R., Knutsen, L. J. S., Lawrence, A., Lerpiniere, J., Misra, A., Porter, R. H. P., Pratt, R. M., Shepherd, R., Upton, R., Ward, S. E., Weiss, S. M., and Williamson, D. S. (2008) Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives Bioorg. Med. Chem. Lett. 18, 2916-2919 (Pubitemid 351608875)
70. Gillespie, R. J., Cliffe, I. A., Dawson, C. E., Dourish, C. T., Gaur, S., Giles, P. R., Jordan, A. M., Knight, A. R., Lawrence, A., Lerpiniere, J., Misra, A., Pratt, R. M., Todd, R. S., Upton, R., Weiss, S. M., and Williamson, D. S. (2008) Antagonists of the human adenosine A2A receptor. Part 2: Design and synthesis of 4-arylthieno[3,2-d]pyrimidine derivatives Bioorg. Med. Chem. Lett. 18, 2920-2923 (Pubitemid 351608876)
71. Gillespi, R. J., Cliffe, I. A., Dawson, C. E., Dourish, C. T., Gaur, S., Jordan, A. M., Knight, A. R., Lerpiniere, J., Misra, A., Pratt, R. M., Roffey, J., Stratton, G. C., Upton, R., Weiss, S. M., and Williamson, D. S. (2008) Antagonists of the human adenosine A2A receptor. Part 3: Design and synthesis of pyrazolo[3,4-d]pyrimidines, pyrrolo[2,3-d]pyrimidines and 6-arylpurines Bioorg. Med. Chem. Lett. 18, 2924-2929 (Pubitemid 351608872)
72. Gillespie, R. J., Bamford, S. J., Botting, R., Comer, M., Denny, S., Gaur, S., Griffin, M., Jordan, A. M., Knight, A. R., Lerpiniere, J., Leonardi, S., Lightowler, S., McAteer, S., Merrett, A., Misra, A., Padfield, A., Reece, M., Saadi, M., Selwood, D. L., Stratton, G. C., Surry, D., Todd, R., Tong, X., Ruston, V., Upton, R., and Weiss, S. M. (2009) Antagonists of the Human A2A Adenosine Receptor. 4. Design, Synthesis, and Preclinical Evaluation of 7-Aryltriazolo[4,5-d]pyrimidines J. Med. Chem. 52, 33-47
73. Vernalis. (2004) Vernalis and Biogen Idec to collaborate on research for Parkinson's disease. Press Release, June 24.
74. 2A receptor antagonist programme for Parkinson's disease with next generation compound. Press Release, July 16.
75. Minetti, P., Tinti, M. O., Carminati, P., Castorina, M., Di Cesare, M. A., Di Serio, S., Gallo, G., Ghirardi, O., Giorgi, F., Giorgi, L., Piersanti, G., Bartoccini, F., and Tarzia, G. (2005) 2- n -Butyl-9-methyl-8-[1,2,3]triazol- 2-yl-9H-purin-6-ylamine and Analogues as A2A Adenosine Receptor Antagonists. Design, Synthesis, and Pharmacological Characterization J. Med. Chem. 48, 6887-6896 (Pubitemid 41533110)
76. Stasi, M. A., Borsini, F., Varani, K., Vincenzi, F., Di Cesare, M. A., Minetti, P., Ghirardi, O., and Carminati, P. (2006) ST 1535: a preferential A2A adenosine receptor antagonist Int. J. Neuropsychopharmacology 9, 575-584 (Pubitemid 44607210)
77. Rose, S., Ramsay Croft, N., and Jenner, P. (2007) The novel adenosine A2a antagonist ST1535 potentiates the effects of a threshold dose of L-dopa in unilaterally 6-OHDA-lesioned rats Brain Res. 1133, 110-114 (Pubitemid 46123239)
78. Tronci, E., Simola, N., Borsini, F., Schintu, N., Frau, L., Carminati, P., and Morelli, M. (2007) Characterization of the antiparkinsonian effects of the new adenosine A2A receptor antagonist ST1535: Acute and subchronic studies in rats Eur. J. Pharmacol. 566, 94-102 (Pubitemid 46782796)
79. Rose, S., Jackson, M. J., Smith, L. A., Stockwell, K., Johnson, L., Carminati, P., and Jenner, P. (2006) The novel adenosine A2a receptor antagonist ST1535 potentiates the effects of a threshold dose of L-DOPA in MPTP treated common marmosets Eur. J. Pharmacol. 546, 82-87 (Pubitemid 44348896)
80. Shook, B. C., Chakravarty, D., Barbay, J. K., Wang, W., Leonard, K., Alford, V., Powell, M., Beauchamp, D. A., Rassnick, S., Scannevin, R., Carroll, K., Wallace, N., Crooke, J., Ault, M., Lampron, L., Westover, L., Rhodes, K., and Jackson, P. F. (2011) Aminomethyl substituted thieno[2,3-d]pyrimidines as adenosine A2A receptor antagonists. Med. Chem. Commun. published online May 19, 2011. DOI: 10.1039/C1MD00082A.
81. McGuinness, B. F., Cole, A. G., Dong, G., Brescia, M.-R., Shao, Y., Henderson, I., Rokosz, L. L., Stauffer, T. M., Mannava, N., Kimble, E. F., Hicks, C., White, N., Wines, P. G., and Quadros, E. (2010) Discovery of 2-aminoimidazopyridine adenosine A2A receptor antagonists Bioorg. Med. Chem. Lett. 20, 6845-6849
82. Flohr, A., Moreau, J. L., Poli, S. M., Riemer, C., and Steward, L. (2005) 4-Hydroxy-4-methyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl- benzothiazol-2-yl)-amide. US 20050261289.
83. Flohr, A. and Riemer, C. (2006) Benzothiazole derivatives. WO 2006008041.
84. Flohr, A. and Riemer, C. (2006) Substituted benzothiazoles. WO 2006008040.
85. Woiwode, T. and Noran, M. (2000) 4-Hydroxy-4-methyl-piperidine-1- carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide for the treatment of post-traumatic stress disorder. PCT Int. Appl. WO 2009015236.
86. Synosis Therapeutics. (2007) Roche and Synosis Therapeutics announce partnership to explore potential of five compounds targeting the central nervous system. Press Release, January 4.
87. Saku, O., Saki, M., Kurokawa, M., Ikeda, K., Takizawa, T., and Uesaka, N. (2010) Synthetic studies on selective adenosine A2A receptor antagonists: Synthesis and structure-activity relationships of novel benzofuran derivatives Bioorg. Med. Chem. Lett. 20, 1090-1093
88. Saku, O., Saki, M., Kurokawa, M., Ikeda, K., Uchida, S.-I., Takizawa, T., and Uesaka, N. (2010) Synthetic studies on selective adenosine A2A receptor antagonists. Part II: Synthesis and structure-activity relationships of novel benzofuran derivatives Bioorg. Med. Chem. Lett. 20, 3768-3771
89. 2A receptor antagonists and their pharmaceutical compositions. PCT Int. Appl. WO 2005040151.
90. Mihara, T., Mihara, K., Yarimizu, J., Mitani, Y., Matsuda, R., Yamamoto, H., Aoki, S., Akahane, A., Iwashita, A., and Matsuoka, N. (2007) Pharmacological characterization of a novel, potent adenosine A1 and A2A receptor dual antagonist, 5-[5-amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H) -one (ASP5854), in models of Parkinson's disease and cognition J. Pharmacol. Exp. Ther. 323, 708-719 (Pubitemid 350005141)
91. Mihara, T., Noda, A., Arai, H., Mihara, K., Iwashita, A., Murakami, Y., Matsuya, T., Miyoshi, S., Nishimura, S., and Matsuoka, N. (2008) Brain adenosine A2A receptor occupancy by a novel A1/A2A receptor antagonist, ASP5854, in rhesus monkeys: relationship to anticataleptic effect J. Nucl. Med. 49, 1183-1188 (Pubitemid 351948029)
92. Mihara, T., Iwashita, A., and Matsuoka, N. (2008) A novel adenosine A1 and A2A receptor antagonist ASP5854 ameliorates motor impairment in MPTP-treated marmosets: Comparison with existing anti-Parkinson's disease drugs Behav. Brain Res. 194, 152-161
93. Sams, A. G., Mikkelsen, G. K., Larsen, M., Torup, L., Brennum, L. T., Schroder, T. J., and Bang-Andersen, B. (2010) Hit-to-lead optimization of a series of carboxamides of ethyl 2-amino-4-phenylthiazole-5-carboxylates as novel adenosine A2A receptor antagonists Bioorg. Med. Chem. Lett. 20, 5241-5244
94. Cole, A. G., Stauffer, T. M., Rokosz, L. L., Metzger, A., Dillard, L. W., Zeng, W., and Henderson, I. (2009) Synthesis of 2-amino-5-benzoyl-4-(2-furyl) thiazoles as adenosine A2A receptor antagonists Bioorg. Med. Chem. Lett. 19, 378-381
95. Zhang, X., Rueter, J. K., Chen, Y., Moorjani, M., Lanier, M. C., Lin, E., Gross, R. S., Tellew, J. E., Williams, J. P., Lechner, S. M., Markison, S., Joswig, T., Malany, S., Santos, M., Castro-Palomino, J. C., Crespo, M. I., Prat, M., Gual, S., Diaz, J.-L., Saunders, J., and Slee, D. H. (2008) Synthesis of N -pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists Bioorg. Med. Chem. Lett. 18, 1778-1783 (Pubitemid 351391849)
96. Slee, D. H., Zhang, X., Moorjani, M., Lin, E., Lanier, M. C., Chen, Y., Rueter, J. K., Lechner, S. M., Markison, S., Malany, S., Joswig, T., Santos, M., Gross, R. S., Williams, J. P., Castro-Palomino, J. C., Crespo, M. I., Prat, M., Gual, S., Diaz, J.-L., Wen, J., O'Brien, Z., and Saunders, J. (2008) Identification of Novel, Water-Soluble, 2-Amino-N-pyrimidin-4-yl Acetamides as A2A Receptor Antagonists with In Vivo Efficacy J. Med. Chem. 51, 400-406 (Pubitemid 351252268)
97. Slee, D. H., Chen, Y., Zhang, X., Moorjani, M., Lanier, M. C., Lin, E., Rueter, J. K., Williams, J. P., Lechner, S. M., Markison, S., Malany, S., Santos, M., Gross, R. S., Jalali, K., Sai, Y., Zuo, Z., Yang, C., Castro-Palomino, J. C., Crespo, M. I., Prat, M., Gual, S., Diaz, J.-L., and Saunders, J. (2008) 2-Amino-N-pyrimidin-4-ylacetamides as A2A Receptor Antagonists: 1. Structure-Activity Relationships and Optimization of Heterocyclic Substituents J. Med. Chem. 51, 1719-1729 (Pubitemid 351438853)
98. Moorjani, M., Luo, Z., Lin, E., Vong, B. G., Chen, Y., Zhang, X., Rueter, J. K., Gross, R. S., Lanier, M. C., Tellew, J. E., Williams, J. P., Lechner, S. M., Malany, S., Santos, M., Crespo, M. I., Diaz, J.-L., Saunders, J., and Slee, D. H. (2008) 2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A2A antagonists with improved solubility and metabolic stability Bioorg. Med. Chem. Lett. 18, 5402-5405
99. Gillespie, R. J., Bamford, S. J., Gaur, S., Jordan, A. M., Lerpiniere, J., Mansell, H. L., and Stratton, G. C. (2009) Antagonists of the human A2A receptor. Part 5: Highly bio-available pyrimidine-4-carboxamides Bioorg. Med. Chem. Lett. 19, 2664-2667
100. Gillespie, R. J., Bamford, S. J., Clay, A., Gaur, S., Haymes, T., Jackson, P. S., Jordan, A. M., Klenke, B., Leonardi, S., Liu, J., Mansell, H. L., Ng, S., Saadi, M., Simmonite, H., Stratton, G. C., Todd, R. S., Williamson, D. S., and Yule, I. A. (2009) Antagonists of the human A2A receptor. Part 6: Further optimization of pyrimidine-4-carboxamides Bioorg. Med. Chem. 17, 6590-6605