Antagonists of the human A2A adenosine receptor. 4. Design, synthesis, and preclinical evaluation of 7-aryltriazolo[4,5-d]pyrimidines

Journal of Medicinal Chemistry

Volumn 52, Issue 1, 2009, Pages 33-47

  Gillespie, Roger J ^a   Bamford, Samantha J ^a   Botting, Ruth ^a   Comer, Mike ^a   Denny, Sarah ^a   Gaur, Suneel ^a   Griffin, Michael ^a   Jordan, Allan M ^a   Knight, Anthony R ^a   Lerpiniere, Joanne ^a   Leonardi, Stefania ^a   Lightowler, Sean ^a   McAteer, Steven ^a   Merrett, Angela ^a   Misra, Anil ^a   Padfield, Antony ^a   Reece, Mark ^a   Saadi, Mona ^a   Selwood, Daniel L ^a   Stratton, Gemma C ^a   Surry, Dominic ^a   Todd, Richard ^a   Tong, Xin ^a   Ruston, Vicki ^a   Upton, Rebecca ^a   Weiss, Scott M ^a   more..

^a Vernalis PLC   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 (4 AMINO 3 METHYLBENZYL) 7 (2 FURYL) 3H [1,2,3]TRIAZOLO[4,5 D]PYRIMIDIN 5 AMINE; 8 AZAPURINE DERIVATIVE; ADENOSINE A2A RECEPTOR ANTAGONIST; BIIB 014; UNCLASSIFIED DRUG; V 2006; ADENOSINE A2A RECEPTOR; AMINE; HALOPERIDOL; PYRIMIDINE; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE;

ARTICLE; CLINICAL TRIAL; DRUG DESIGN; DRUG EFFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; NONHUMAN; PARKINSON DISEASE; REACTION ANALYSIS; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; CHEMICAL STRUCTURE; CHEMICALLY INDUCED DISORDER; CHEMISTRY; CLASSIFICATION; DRUG ANTAGONISM; DRUG SCREENING; METABOLISM; MOUSE; NEUROLOGIC DISEASE; RAT; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

AMINES; ANIMALS; AZOLES; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; GAIT DISORDERS, NEUROLOGIC; HALOPERIDOL; HUMANS; MICE; MOLECULAR STRUCTURE; PYRIMIDINES; RATS; RECEPTOR, ADENOSINE A2A; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 59449094359     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm800961g     Document Type: Article

References (48)

1. Jankovic, J. Parkinson's disease: clinical features and diagnosis. J. Neurol., Neurosurg. Psychiatry 2008, 79 (4), 368-376.
2. Boller, F.; Mizutani, T.; Roessmann, U.; Gambetti, P. Parkinson disease, dementia, and Alzheimer disease: clinicopathological correlations. Ann. Neurol. 1980, 7 (4), 329-335.
3. Blandini, F.; Porter, R. H. P.; Greenamyre, J. T. Glutamate and Parkinson's disease. Mol. Neurobiol. 1996, 12 (1), 73-94.
4. -chronic treatment with L-dopa. New Engl. J. Med. 1969, 280 (7), 337-345.
5. Barbeau, A. L-Dopa therapy in Parkinson's disease: a critical review of nine years' experience. Can. Med. Assoc. J. 1969, 101 (13), 59-68.
6. Rinne, U. K. Problems associated with long-term levodopa treatment of Parkinson's disease. Acta Neurol. Scand., Suppl. 1983, 95, 19-26.
7. 2A receptor expression in striatal neurons: implications for basal ganglia pathophysiology. Drug Dev. Res 1993, 28 (3), 381-385.
8. 2A receptors. Prog. Neurobiol. 1999, 59 (4), 355-396.
9. 2A receptor antagonists in Parkinson's disease. Pharmacol. Ther 2005, 105 (3), 267-310.
10. 2A receptor antagonist treatment of Parkinson's disease. Neurology 2003, 61 (3), 293-296.
11. 2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in Parkinsonian monkeys. Ann. Neurol. 1998, 43 (4), 507-513.
12. 2 receptors in rat striatal membranes. Proc. Natl. Acad. Sci. U.S.A. 1991, 88 (16), 7238-7241.
13. 2 Receptor Interactions in the Basal Ganglia: Analysis from the Network to the Molecular Level. In Adenosine and Adenine Nucleotides: From Molecular Biology to Integrative Physiology, Proceedings of the 5th International Symposium on Adenosine and Adenine Nucleotides, Philadelphia, PA, May 9-13, 1994; Springer: Berlin, 1995; pp 499-507.
14. Ferre, S.; Fredholm, B. B.; Morelli, M.; Popoli, P.; Fuxe, K. Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci. 1997, 20 (10), 482-487.
15. 2A receptor antagonists. Life Sci. 2005, 77 (26), 3259-3267.
16. 2A receptors and basal ganglia physiology. Prog. Neu- robiol. 2007, 83 (5), 277-292.
17. 2A adenosine receptor inactivation in a model of Parkinson's disease. J. Neurosci. 2001, 21 (10), RC143/1-RC143/6.
18. 2A receptors and neuroprotection. Ann. N.Y. Acad. Sci. 1997, 825 (Neuroprotective Agents), 30-48.
19. Rabasseda, X.; Sorbera, L. A.; Martin, L.; Leeson, P. A.; Castaner, J. KW-6002. Drugs Future 2001, 26 (1), 20-24.
20. 2A receptor antagonist istradefylline (KW-6002) reduces "off time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann. Neurol. 2008, 63 (3), 295-302.
21. http://www.kyowa.co.jp/eng/netext/er060307.htm.
22. http://www.kyowa.co.jp/eng/netext/er080228-01.htm.
23. 2A adenosine receptor antagonists with 8-styrylxanthine structure: potential drugs for Parkinson's disease. J. Org. Chem. 2004, 69 (10), 3308-3318.
24. Knutsen, L. J. S.; Weiss, S. M. KW-6002, Kyowa Hakko Kogyo. Curr. Opin. Invest. Drugs 2001, 2 (5), 668-673.
25. 2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4- methanone derivatives. Bioorg. Med. Chem. Lett. 2008, 18 (9), 2916-2919.
26. 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.; Williamson, D. S. Antagonists of the human adenosine A2A receptor. Part 2: Design and synthesis of 4-arylthieno[3,2-d]pyrimidine derivatives. Bioorg. Med. Chem. Lett. 2008, 18 (9), 2920-2923.
27. 2A receptor. Part 3: Design and synthesis of pyrazolo[3,4-d]pyrimidines, pyr- rolo[2,3-d] pyrimidines and 6-arylpurines. Bioorg. Med. Chem. Lett. 2008, 18 (9), 2924-2929.
28. Gillespie, R. J.; Lerpiniere, J.; Gaur, S.; Bamford, S. J.; Stratton, G. C.; Leonardi, S.; Weiss, S. M. Preparation of Triazolo[4,5-d]pyrimidines as Purinergic Receptor Antagonists. PCT Int. Appl. WO2002055083, 2002.
29. Fulmer, S. Y.; Clayton, J. D.; Allen O'Dell, C.; Montgomery, J. A. Triazolo[4,5-d]pyrimidines. II. O-Substituted derivatives of 8-azagua- nine and 8-azahypoxanthine. J. Org. Chem. 1962, 27, 4518-4523.
30. O'Brien, D. E.; Baiocchi, F.; Robins, R. K.; Cheng, C. C. Pyrimidines. XI. J. Med. Chem. 1963, 6 (5), 467-471.
31. O'Brien, D. E.; Cheng, C. C.; Pfleiderer, W. Pyrimidines. XVIII. 2,4- Diamino-5-nitro-6-arylaminopyrimidines. Nitration study of 2,4-diamino-6- chloropyrimidine and a literature correction. J. Med. Chem. 1966, 9 (4), 573-575.
32. Meier, R. Preparation of 7-Amino-3-benzyl-3H-1,2,3-triazolo[4,5- d]pyrimidines as Anticonvulsants. Eur. Pat. Appl. EP288431, 1988.
33. 13C NMR data for both regioisomers of selected compounds with the known N-3 regioisomer 13and the analogous derivatives 14-20. Further confirmation was additionally obtained by synthesis of selected derivatives by the unambiguous route employed for compounds 46 and 47, as detailed in Scheme 7.
34. Borroni, E. M.; Huber-Trottmann, G.; Kilpatrick, G. J.; Norcross, R. D. Preparation of Pyrimidinamines and Pyridinamines as Adenosine Receptor Modulators for Treatment of CNS Disorders. PCT Int. Appl. WO2001062233, 2001.
35. Bentley, S. J.; Milner, D. J. Conjugate addition of Grignard reagents to para-substituted nitrobenzenes. J. Organomet. Chem. 1993, 447 (1), 1-3.
36. Sun, J.-H.; Teleha, C. A.; Yan, J.-S.; Rodgers, J. D.; Nugiel, D. A. Efficient synthesis of 5-(bromomethyl)- and 5-(aminomethyl)-1-THP- indazole. J. Org. Chem. 1997, 62 (16), 5627-5629.
37. Binding assays were conducted as described in the following: Weiss, S. M.; Benwell, K.; Cliffe, I. A.; Gillespie, R. J.; Knight, A. R.; Lerpiniere, J.; Misra, A.; Pratt, R. M.; Revell, D.; Upton, R.; Dourish, C. T. Neurology 2003, 61 (11, Suppl. 6), S101.
38. Bezard, E.; Imbert, C.; Gross, C. E. Experimental models of Parkinson's disease: from the static to the dynamic. Rev. Neurosci. 1998, 9 (2), 71-90.
39. Mandhane, S. N.; Chopde, C. T.; Ghosh, A. K. Adenosine A2 receptors modulate haloperidol-induced catalepsy in rats. Eur. J. Pharmacol. 1997, 328 (2/3), 135-141.
40. Broughton, H. B.; Watson, I. A. Selection of heterocycles for drug design. J. Mol. Graphics Modell. 2004, 23 (1), 51-58.
41. Dalvie, D. K.; Kalgutkar, A. S.; Khojasteh-Bakht, S. C.; Obach, R. S.; O Donnell, J. P. Biotransformation reactions of five-membered aromatic heterocyclic rings. Chem. Res. Toxicol. 2002, 15 (3), 269-299.
42. 2A antagonists using database mining and molecular similarity approaches. Bioorg. Med. Chem. Lett. 2006, 16 (23), 599-5997.
43. Maximal aqueous solubility was determined in a phosphate buffered saline solution containing 2.5% DMSO solution.
44. Porter, R. H. P.; Benwell, K. R.; Lamb, H.; Malcolm, C. S.; Allen, N. H.; Revell, D. F.; Adams, D. R.; Sheardown, M. J. Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells. Br. J. Pharmacol. 1999, 128, 13-20.
45. Artursson, P.; Karlsson, J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun. 1991, 175 (3), 880-885.
46. -1.
47. http://www.cerep.fr/Cerep/Users/pages/Catalog/Profiles/catalog.asp.
48. Irwin, S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia 1968, 13 (3), 222-257.