8-Benzyltetrahydropyrazino[2,1-f]purinediones: Water-soluble tricyclic xanthine derivatives as multitarget drugs for neurodegenerative diseases

ChemMedChem

Volumn 9, Issue 8, 2014, Pages 1704-1724

  Brunschweiger, Andreas ^a,c   Koch, Pierre ^a,d   Schlenk, Miriam ^a   Pineda, Felipe ^a   Küppers, Petra ^a   Hinz, Sonja ^a   Köse, Meryem ^a   Ullrich, Stefan ^a   Hockemeyer, Jörg ^a   Wiese, Michael ^a   Heer, Jag ^b   Müller, Christa E ^a  

^a UNIVERSITY OF BONN   (Germany)

^b Preclinical CNS Research   (Belgium)

^c TU DORTMUND UNIVERSITY   (Germany)

^d UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

adenosine receptors; antagonists; inhibitors; monoamine oxidases; multitarget drugs; neurodegenerative diseases

Indexed keywords

1,3 DIMETHYL 8 (THIOPHEN 3 YL) 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 1,3 DIMETHYL 8 [3 (THIAZOL 2 YL)BENZYL] 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 1,3 DIMETHYL 8 [3 (THIOPHEN 2 YL)BENZYL] 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 7 (2 BROMOETHYL) 8 (HYDROXYMETHYL) 1,3 DIMETHYL 1H PURINE 2,6(3H,7H) DIONE; 8 (2 BROMOBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO [2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (2 CHLOROBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4 (1H,3H) DIONE; 8 (2 FLUOROBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F ]PURINE 2,4(1H,3H) DIONE; 8 (2 METHOXYBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (2,4 DICHLORO 5 FLUOROBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F ]PURINE (1H,3H) DIONE; 8 (3 BROMOBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (3 CHLOROBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (3 FLUOROBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (3 IODOBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (3 METHOXYBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (4 BROMOBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (4 CHLOROBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (4 FLUOROBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 (4 METHOXYBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 BENZYL 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F ]PURINE 2,4(1H,3H) DIONE; 8 BENZYLTETRAHYDROPYRAZINO[2,1 F ]PURINEDIONE; 8 [2 (TRIFLUOROMETHYL)BENZYL] 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 [3 (1H PYRROL 1 YL)BENZYL] 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; 8 [3 (TRIFLUOROMETHYL)BENZYL] 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; ADENOSINE A1 RECEPTOR ANTAGONIST; ADENOSINE A2 RECEPTOR ANTAGONIST; MONOAMINE OXIDASE A INHIBITOR; MONOAMINE OXIDASE B INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; XANTHINE DERIVATIVE; [8 (3,4 DICHLOROBENZYL) 1,3 DIMETHYL 6,7,8,9 TETRAHYDROPYRAZINO[2,1 F]PURINE 2,4(1H,3H) DIONE; AMINE OXIDASE (FLAVIN CONTAINING); MONOAMINE OXIDASE INHIBITOR; WATER;

ANIMAL EXPERIMENT; ARTICLE; BLOOD BRAIN BARRIER; DEGENERATIVE DISEASE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG SOLUBILITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; LIVER MICROSOME; MOLECULAR LIBRARY; NONHUMAN; PLASMA PROTEIN BINDING; PRIORITY JOURNAL; RAT; STRUCTURE ACTIVITY RELATION; ANIMAL; CHEMISTRY; HALF LIFE TIME; METABOLISM; NEURODEGENERATIVE DISEASES; SOLUBILITY;

ANIMALS; HALF-LIFE; HUMANS; MICROSOMES, LIVER; MONOAMINE OXIDASE; MONOAMINE OXIDASE INHIBITORS; NEURODEGENERATIVE DISEASES; RATS; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; WATER; XANTHINES;

EID: 84905197455     PISSN: 18607179     EISSN: 18607187     Source Type: Journal    
DOI: 10.1002/cmdc.201402082     Document Type: Article

References (62)

1. B. B. Fredholm, A. P. IJzerman, K. A. Jacobson, K.-N. Klotz, J. Linden, Pharmacol. Rev. 2001, 53, 527-552.
2. B. B. Fredholm, A. P. IJzerman, K. A. Jacobson, J. Linden, C. E. Müller, Pharmacol. Rev. 2011, 63, 1-34.
3. A. K. Dhalla, J. C. Shryock, R. Shreeniwas, L. Belardinelli, Curr. Top. Med. Chem. 2003, 3, 369-385.
4. J. A. Ribeiro, A. M. Sebastião, A. de Mendonça, Prog. Neurobiol. 2002, 68, 377-392.
5. S. Ferré, B. B. Fredholm, M. Morelli, P. Popoli, K. Fuxe, Trends Neurosci. 1997, 20, 482-487.
6. S. Ferré, C. Quiroz, M. Orru, X. Guitart, G. Navarro, A. Cortés, V. Casadõ, E. I. Canela, C. Lluis, R. Franco, Front. Neuroanat. 2011, 5, 35.
7. J. Bonaventura, A. J. Rico, E. Moreno, S. Sierra, M. Sánchez, N. Luquin, D. Farré, C. E. Müller, E. Martínez-Pinilla, A. Cortés, J. Mallol, M. T. Armentero, A. Pinna, E. I. Canela, C. Lluís, P. J. McCormick, J. L. Lanciego, V. Casadõ, R. Franco, Neuropharmacology 2014, 79, 90-100.
8. S. Duty, P. Jenner, Br. J. Pharmacol. 2011, 164, 1357-1391.
9. M. T. Armentero, A. Pinna, S. Ferré, J. L. Lanciego, C. E. Müller, R. Franco, Pharmacol. Ther. 2011, 132, 280-299.
10. C. E. Muller, S. Ferré, Recent Pat. CNS Drug Discovery 2007, 2, 1-21.
11. A. Kachroo, M. A. Schwarzschild, Ann. Neurol. 2012, 71, 278-282.
12. O. P. DallIgna, L. O. Porciúncula, D. O. Souza, R. A. Cunha, D. R. Lara, Br. J. Pharmacol. 2003, 138, 1207-1209.
13. L. Yu, H. Y. Shen, J. E. Coelho, I. M. Araujo, Q. Y. Huang, Y. J. Day, N. Rebola, P. M. Canas, E. K. Rapp, J. Ferrara, D. Taylor, C. E. Müller, J. Linden, R. A. Cunha, J. F. Chen, Ann. Neurol. 2008, 63, 338-346.
14. J. F. Chen, Y. Chern, Handb. Exp. Pharmacol. 2011, 200, 267-310.
15. M. B. H. Youdim, D. Edmondson, K. F. Tipton, Nat. Rev. Neurosci. 2006, 7, 295-309.
16. J. G. Fiedorowicz, K. L. Swartz, J. Psychiatr. Practice 2004, 10, 239-248.
17. M. B. H. Youdim, Y. S. Bakhle, Br. J. Pharmacol. 2006, 147, S 287 -S 296.
18. A. Macedo, E. Leiria, A. Filipe, Clin. Drug Invest. 2011, 31, 61-71.
19. Parkinson Study Group, Ann. Neurol. 1996, 40, 99-107.
20. Parkinson Study Group, Arch. Neurol. 2005, 62, 241-248.
21. P. Riederer, L. Lachenmayer, G. Laux, Curr. Med. Chem. 2004, 11, 2033-2043.
22. G. R. Zimmermann, J. Lehár, C. T. Keith, Drug Discovery Today 2007, 12, 34-42.
23. W. J. Geldenhuys, C. J. Van der Schyf, Curr. Med. Chem. 2013, 20, 1662-1672.
24. P. Dunkel, C. L. Chai, B. Sperlágh, B. B. Huleatt, P. Mátyus, Expert Opin. Invest. Drugs 2012, 21, 1267-1308.
25. M. Bajda, N. Guzior, M. Ignasik, B. Malawska, Curr. Med. Chem. 2011, 18, 4949-4975.
26. D. Schubert, P. Maher, Future Med. Chem. 2012, 4, 1681-1688.
27. F. Prati, E. Uliassi, M. L. Bolognesi, Med. Chem. Commun. 2014, DOI:.
28. T. Mihara, K. Mihara, J. Yarimizu, Y. Mitani, R. Matsuda, H. Yamamoto, S. Aoki, A. Akahane, A. Iwashita, N. Matsuoka, J. Pharmacol. Exp. Ther. 2007, 323, 708-719.
29. T. Mihara, A. Iwashita, N. Matsuoka, Behav. Brain Res. 2008, 194, 152-161.
30. B. C. Shook, S. Rassnick, M. C. Osborne, S. Davis, L. Westover, J. Boulet, D. Hall, K. C. Rupert, G. R. Heintzelman, K. Hansen, D. Chakravarty, J. L. Bullington, R. Russell, S. Branum, K. M. Wells, S. Damon, S. Youells, X. Li, D. A. Beauchamp, D. Palmer, M. Reyes, K. Demarest, Y. T. Tang, K. Rhodes, P. F. Jackson, J. Med. Chem. 2010, 53, 8104-8115.
31. B. C. Shook, P. F. Jackson, ACS Chem. Neurosci. 2011, 2, 555-567.
32. R. N. Takahashi, F. A. Pamplona, R. D. S. Prediger, Front. Biosci. 2008, 13, 2614-2632.
33. C. E. Müller, K. A. Jacobson, Handb. Exp. Pharmacol. 2011, 200, 151-199.
34. C. E. Müller, K. A. Jacobson, Biochim. Biophys. Acta Biomembr. 2011, 1808, 1290-1308.
35. G. W. Ross, R. D. Abbott, H. Petrovitch, D. M. Morens, A. Grandinetti, K. H. Tung, C. M. Tanner, K. H. Masaki, P. L. Blanchette, J. D. Curb, J. S. Popper, L. R. White, JAMA J. Am. Med. Assoc. 2000, 283, 2674-2679.
36. G. W. Arendash, C. Cao, J. Alzheimers Dis. 2010, 20, S 117 -S 126.
37. T. Mihara, A. Noda, H. Arai, K. Mihara, A. Iwashita, Y. Murakami, T. Matsuya, S. Miyoshi, S. Nishimura, N. Matsuoka, J. Nucl. Med. 2008, 49, 1183-1188.
38. J. F. Chen, S. Steyn, R. Staal, J. P. Petzer, K. Xu, C. J. Van der Schyf, K. Castagnoli, P. K. Sonsalla, N. Castagnoli, Jr., M. A. Schwarzschild, J. Biol. Chem. 2002, 277, 36040-36044.
39. J. P. Petzer, N. Castagnoli, Jr., M. A. Schwarzschild, J. F. Chen, C. J. Van der Schyf, Neurotherapeutics 2009, 6, 141-151.
40. S. Rivara, G. Piersanti, F. Bartoccini, G. Diamantini, D. Pala, T. Riccioni, M. A. Stasi, W. Cabri, F. Borsini, M. Mor, G. Tarzia, P. Minetti, J. Med. Chem. 2013, 56, 1247-1261.
41. B. Grahner, S. Winiwarter, W. Lanzner, C. E. Müller, J. Med. Chem. 1994, 37, 1526-1534.
42. A. M. Hayallah, J. Sandoval-Ramírez, U. Reith, U. Schobert, B. Preiss, B. Schumacher, J. W. Daly, C. E. Müller, J. Med. Chem. 2002, 45, 1500-1510.
43. O. Weinreb, T. Amit, O. Bar-Am, M. B. Youdim, Curr. Drug Targets 2012, 13, 483-494.
44. M. Yáñez, D. Viña, Curr. Top. Med. Chem. 2013, 13, 1692-1706.
45. A. Drabczyńska, B. Schumacher, C. E. Müller, J. Karolak-Wojciechowska, B. Michalak, E. Pȩkala, K. Kiec̈-Kononowicz, Eur. J. Med. Chem. 2003, 38, 397-402.
46. A. Drabczyńska, C. E. Müller, S. K. Lacher, B. Schumacher, J. Karolak-Wojciechowska, A. Nasal, P. Kawczak, O. Yuzlenko, E. Pȩkala, K. Kiec̈-Kononowicz, Bioorg. Med. Chem. 2006, 14, 7258-7281.
47. A. Drabczyńska, C. E. Müller, J. Karolak-Wojciechowska, B. Schumacher, A. Schiedel, O. Yuzlenko, K. Kiec̈-Kononowicz, Bioorg. Med. Chem. 2007, 15, 5003-5017.
48. A. Drabczyńska, C. E. Müller, A. Schiedel, B. Schumacher, J. Karolak-Wojciechowska, A. Fruziński, W. Zobnina, O. Yuzlenko, K. Kiec̈-Kononowicz, Bioorg. Med. Chem. 2007, 15, 6956-6974.
49. A. Drabczyńska, O. Yuzlenko, M. Köse, M. Paskaleva, A. C. Schiedel, J. Karolak-Wojciechowska, J. Handzlik, T. Karcz, K. Kuder, C. E. Müller, K. Kiec̈-Kononowicz, Eur. J. Med. Chem. 2011, 46, 3590-3607.
50. P. Koch, R. Akkari, A. Brunschweiger, M. Schlenk, T. Borrmann, M. Schlenk, P. Küppers, M. Köse, H. Radjainia, J. Hockemeyer, A. Drabczyńska, K. Kiec̈-Kononowicz, C. E. Müller, Bioorg. Med. Chem. 2013, 21, 7435-7452.
51. A. Drabczyńska, M. Zygmunt, J. Sapa, B. Filipek, C. E. Müller, K. Kiec̈-Kononowicz, Arch. Pharm. 2011, 344, 20-27.
52. E. Carstens, J. Donat, F. Hauschild, (VEB Chemische Werke Radebeul), Ger. Pat. No. DE1086707A, 1960.
53. B. Gong, J. P. Klein, M. Coon, (Cell Therapeutics Inc.), US Pat. No. US2002/0103211A1, 2000.
54. C. E. Müller, R. Sauer, U. Geis, W. Frobenius, P. Talik, M. Pawlowski, Arch. Pharm. 1997, 330, 181-189.
55. K. N. Klotz, J. Hessling, J. Hegler, C. Owman, B. Kull, B. B. Fredholm, M. J. Lohse, Naunyn-Schmiedebergs Arch. Pharmacol. 1997, 357, 1-9.
56. C. E. Müller, J. Maurinsh, R. Sauer, Eur. J. Pharm. Sci. 2000, 10, 259-265.
57. T. Borrmann, S. Hinz, D. C. G. Bertarelli, W. Li, N. C. Florin, A. B. Scheiff, C. E. Müller, J. Med. Chem. 2009, 52, 3994-4006.
58. C. E. Müller, M. Diekmann, M. Thorand, V. Ozola, Bioorg. Med. Chem. Lett. 2002, 12, 501-503.
59. A. Stößel, M. Schlenk, S. Hinz, P. Küppers, J. Heer, M. Gütschow, C. E. Müller, J. Med. Chem. 2013, 56, 4580-4596.
60. C. E. Müller, T. Scior, Pharm. Acta Helv. 1993, 68, 77-111.
61. D. C. G. Bertarelli, M. Diekmann, A. M. Hayallah, D. Rüsing, J. Iqbal, B. Preiss, E. J. Verspohl, C. E. Müller, Purinergic Signalling 2006, 2, 559-571.
62. L. Yan, D. C. G. Bertarelli, A. M. Hayallah, H. Meyer, K.-N. Klotz, C. E. Müller, J. Med. Chem. 2006, 49, 4384-4391.