Potent and selective adenosine A2A receptor antagonists: [1,2,4]-triazolo[4,3-c]pyrimidin-3-ones

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 8, 2011, Pages 2497-2501

  Harris, Joel M ^a   Neustadt, Bernard R ^a   Zhang, Hongtao ^a   Lachowicz, Jean ^a   Cohen Williams, Mary ^a   Varty, Geoff ^a   Hao, Jinsong ^a   Stamford, Andrew W ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

A2A; A2A antagonist; A2A receptor; Adenosine; Adenosine receptor; Parkinson's disease

Indexed keywords

1,2,4 TRIAZOLO[4,3 C]PYRIMIDIN 3 ONE; ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR ANTAGONIST; PYRIMIDINE DERIVATIVE; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; NONHUMAN; PARKINSON DISEASE; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ADENOSINE A2 RECEPTOR ANTAGONISTS; HUMANS; PARKINSON DISEASE; PYRIMIDINONES; RECEPTOR, ADENOSINE A2A; STRUCTURE-ACTIVITY RELATIONSHIP;

HUMAN ECHOVIRUS 1;

EID: 79953274958     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.02.045     Document Type: Article

References (37)

1. S. Ferre, G. von Euler, B. Johansson, B.B. Fredholm, and K. Fuxe Proc. Natl. Acad. Sci. U.S.A. 88 1991 7238
2. 2A Receptors in Parkinson's Disease and Other CNS Disorders.
3. J. Jankovic Chin. Med. J. 114 2001 227
4. J. Jankovic Mov. Disord. 20 2005 S11
5. 2A antagonists see: G. Cristalli, C. Lambertucci, G. Marucci, R. Volpini, and D. Dal Ben Curr. Pharmaceutical Des. 14 2008 1525
6. O. Yuzlenko, and K. Kiec-Kononowicz Curr. Med. Chem. 13 2006 3609
7. M.A. Schwarzschild, L. Agnati, K. Fuxe, J.-F. Chen, and M. Morelli Trends Neurosci. 29 2006 647
8. K. Xu, E. Bastia, and M. Schwarzschild Pharmacol. Ther. 105 2005 267
9. H. Kase, A. Mori, and P. Jenner Drug Discov. Today 1 2004 51
10. B.B. Fredholm, M.P. Abbracchio, G. Burnstock, J.W. Daly, T.K. Harden, K.A. Jacobson, P. Leff, and M. Williams Pharmacol. Rev. 46 1994 143
11. K.A. Jacobson, P.J.M. van Galen, and M. Williams J. Med. Chem. 35 1992 4007
12. C.E. Muller Drugs Future 25 2000 1043
13. H. Kase Biosci., Biotechnol., Biochem. 65 2001 1447
14. P. Jenner Neurology 61 2003 S32
15. P. Jenner Expert Opin. Investig. Drugs 14 2005 729
16. W. Bara-Himenez, A. Sherzai, T. Dimitrova, A. Favit, F. Bibbiani, M. Gillespie, M.J. Morris, M.M. Mouradian, and T.N. Chase Neurology 61 2003 293
17. R.A. Hauser, J.P. Hubble, and D.D. Truong Neurology 61 2003 297
18. B.R. Neustadt, J. Hao, N. Lindo, W.J. Greenlee, A.W. Stamford, D. Tulshian, E. Ongini, J. Hunter, A. Monopoli, R. Bertorelli, C. Foster, L. Arik, J. Lachowicz, K. Ng, and K. Feng Bioorg. Med. Chem. Lett. 17 2007 1376
19. 2A receptor antagonists are summarized in: U. Shah, and R. Hodgson Curr. Opin. Drug Discov. Devel. 13 2010 466
20. B.R. Neustadt, H. Liu, J. Hao, W.J. Greenlee, W. Stamford, C. Foster, L. Arik, J. Lachowicz, H. Zhang, R. Bertorelli, S. Fredduzzi, G. Varty, M. Cohen-Williams, and K. Ng Bioorg. Med. Chem. Lett. 19 2009 967
21. M. Mooranji, Z. Luo, E. Lin, B.G. Vong, Y. Chen, X. Zhang, J.K. Rueter, R.S. Gross, M.C. Lanier, J.E. Tellew, J.P. Williams, S.M. Lechner, S. Malany, M. Santos, M.I. Crespo, J.-L. Diaz, J. Saunders, and D.H. Slee Bioorg. Med. Chem. Lett. 18 2008 5402
22. A.G. Cole, T.M. Stauffer, L.L. Rokosz, A. Metzger, L.W. Dillard, W. Zeng, and I. Henderson Bioorg. Med. Chem. Lett. 19 2009 378
23. Y. Shao, A.G. Cole, M.-R. Brescia, L.-Y. Qin, J. Duo, T.M. Stauffer, L.L. Rokosz, B.F. McGuinness, and I. Henderson Bioorg. Med. Chem. Lett. 19 2009 1399
24. M.C. Lanier, M. Moorjani, Z. Luo, Y. Chen, E. Lin, J.E. Tellew, X. Zhang, J.P. Williams, R.S. Gross, S.M. Lechner, S. Markison, T. Joswig, W. Kargo, J. Piercey, M. Santos, S. Malany, M. Zhao, R. Petroski, M.I. Crespo, J.-L. Diaz, J. Saunders, J. Wen, Z. O'Brien, K. Jalali, A. Madan, and D.H. Slee J. Med. Chem. 52 2009 709
25. R.J. Gillespie, S.J. Bamford, S. Gaur, A.M. Jordan, J. Lerpiniere, H.L. Mansell, and G.C. Stratton Bioorg. Med. Chem. Lett. 19 2009 2664
26. J.J. Matasi, J.P. Caldwell, H. Zhang, A. Fawzi, M.E. Cohen-Williams, G.B. Varty, and D.B. Tulshian Bioorg. Med. Chem. Lett. 15 2005 3670
27. Z. Zhang, J.E. Tellew, Z. Luo, M. Moorjani, E. Lin, M.C. Lanier, Y. Chen, J.P. Williams, J. Saunders, S.M. Lechner, S. Markison, T. Joswig, R. Petroxki, J. Piercey, W. Kargo, S. Malany, M. Santos, R.S. Gross, J. Wen, K. Jalali, Z. O'Brien, C.E. Stotz, M.I. Crespo, J.-L. Diaz, and D.H. Slee J. Med. Chem 51 2008 7099
28. A.S. Kalgutkar, and J.R. Soglia Exp. Opin. Drug Metab. Toxicol 1 2005 91
29. D.K. Dalvie, A.S. Kalgutkar, S.C. Khojasteh-Bakht, R.S. Obach, and J.P. O'Donnell Chem. Res. Toxicol 15 2002 269
30. (a) The solubility of preladenant as the crystalline free base in water was 0.2 μM at native pH (5.1). A single measurement at pH 7.4 gave solubility below 10 ng/mL. (b) A detailed description of the solubility assay is provided in: U. Shah, C.D. Boyle, S. Chackalamannil, B.R. Neustadt, N. Lindo, W.J. Greenlee, C. Foster, L. Arik, Y. Zhai, K. Ng, S. Wang, A. Monopoli, and J.E. Lachowicz Bioorg. Med. Chem. Lett 18 2008 4199 Ref. 13
31. Previous work on this ring system for use as CB1 receptor antagonists is disclosed in: Gu, G.; Mikkilineni, A. B.; Sher, P. M.; Murugesan, N.; Gu, Z. U. S. Pat. Appl. Pub. 2006/0287341 A1.
32. 3, 400 MHz) δ 7.93 (s, 1H), 7.42-7.28 (m, 6H), 5.81 (d, J = 16 Hz, 1H), 5.05 (s, 2H), 4.93 (d, J = 8.8 Hz, 1H).
33. 2A receptors did not differ from affinity for the human receptor.
34. Inhibition of haloperidol-induced catalepsy is an in vivo assay used to evaluate Parkinson's drugs (>30% inhibition is considered to be active in this assay). Procedure described in: Ref 11.
35. Synthesis of compound 15 disclosed in: Neustadt, B. R.; Hao, J.; Liu, H.; Boyle, C. D.; Chackalamannil, S.; Shah, U.; Stamford, A.; Harris, J. M. U.S. 2005/0239795 A1.
36. Compounds 17, 18, and 37 were the result of DBU induced elimination of the appropriate chloroethyl-derivative.
37. Procedure described in: K.A. Cox, K. Dunn-Meynell, W.A. Korfmacher, L. Broske, A.A. Nomeir, C.-C. Lin, M.N. Cayen, and W.H. Barr Drug Discov. Today 4 1999 232