Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 8, 2012, Pages 2932-2937

  Adam, Julia M ^a   Clark, John K ^a   Davies, Keneth ^a   Everett, Kathryn ^a   Fields, Ruth ^a   Francis, Stuart ^a   Jeremiah, Fiona ^a   Kiyoi, Takao ^a   Maidment, Maurice ^a   Morrison, Angus ^a   Ratcliffe, Paul ^a   Prosser, Alan ^a   Schulz, Jurgen ^a   Wishart, Grant ^a   Baker, James ^a   Boyce, Susan ^a   Campbell, Robert ^a   Cottney, Jean E ^a   Deehan, Maureen ^a   Martin, Iain ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Cannabinoid; CB1; Peripherally restricted

Indexed keywords

CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR AGONIST; LBP 1; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CATALEPSY; DRUG DESIGN; DRUG PENETRATION; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; MOUSE; NEUROPATHIC PAIN; NONHUMAN; RAT;

ANIMALS; BRAIN; CACO-2 CELLS; DRUG DESIGN; HUMANS; INDOLES; MICE; NEURALGIA; OXADIAZOLES; RATS; RECEPTOR, CANNABINOID, CB1;

RODENTIA;

EID: 84859440850     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.02.048     Document Type: Article

References (41)

1. Y. Cheng, and S.A. Hitchcock Expert Opin. Investig. Drugs 16 2007 951
2. R.N. Kumar, W.A. Chambers, and R.G. Pertwee Anaesthesia 1059 2001 56
3. A.C. Howlett, F. Barth, T.I. Bonner, G. Cabral, P. Casellas, W.A. Devane, C.C. Felder, M. Herkenham, K. Mackie, B.R. Martin, R. Mechoulam, and R.G. Pertwee Pharmacol. Rev. 54 2002 161
4. K. Mackie Annu. Rev. Pharmacol. Toxicol. 46 2006 101
5. S. Peat Int. J. Palliat. Nurs. 16 2010 481
6. M.P. Barnes Expert Opin. Pharmacother. 7 2006 607
7. A.S.C. Rice Nat. Clin. Pract. Neurol. 4 2008 654
8. L. Zuurman, P.C.C.M. Passier, M.L. de Kam, H.J. Kleijn, A.F. Cohen, and J.M.A. van Gerven J. Psychopharmacol. 23 2009 633
9. D. Bridges, A.S.C. Rice, M. Egertova, M.R. Elphick, J. Winter, and G.J. Michael Neuroscience 119 2003 803
10. J.D. Richardson, S. Kilo, and K.M. Hargreaves Pain 75 1998 111
11. A. Fox, A. Kesingland, C. Gentry, K. McNair, S. Patel, L. Urban, and I. James Pain 92 2001 91
12. C.Z. Zhu, J.P. Mikusa, Y. Fan, P.R. Hollingsworth, M. Pai, P. Chandran, A.V. Daza, B.B. Yao, M.J. Dart, M.D. Meyer, M.W. Decker, G.C. Hsieh, and P. Honore Br. J. Pharmacol. 157 2009 645
13. N. Agarwal, P. Pacher, I. Tegeder, F. Amaya, C.E. Constantin, G.J. Brenner, T. Rubino, C.W. Michalski, G. Marsicano, K. Monory, K. Mackie, C. Marian, S. Batkai, D. Parolaro, M.J. Fischer, P. Reeh, G. Kunos, M. Kress, B. Lutz, C.J. Woolf, and R. Kuner Nat. Neurosci. 10 2007 870
14. A. Fox, and S. Bevan Expert Opin. Investig. Drugs 14 2005 695
15. B.W. Trotter, K.K. Nanda, C.S. Burgey, C.M. Potteiger, J.Z. Deng, A.I. Green, J.C. Hartnett, N.R. Kett, Z. Wu, D.A. Henze, K. Della Penna, R. Desai, M.D. Leitl, W. Lemaire, R.B. White, S. Yeh, M.O. Urban, S.A. Kane, G.D. Hartman, and M.T. Bilodeau Bioorg. Med. Chem. Lett. 21 2011 2354
16. E.K. Dziadulewicz, S.J. Bevan, C.T. Brain, P.R. Coote, A.J. Culshaw, A.J. Davis, L.J. Edwards, A.J. Fisher, A.J. Fox, C. Gentry, A. Groarke, T.W. Hart, W. Huber, I.F. James, A. Kesingland, L. La Vecchia, Y. Loong, I. Lyothier, K. McNair, C. O'Farrell, M. Peacock, R. Portmann, U. Schopfer, M. Yaqoob, and J. Zadrobilek J. Med. Chem. 50 2007 3851
17. T. Kimura, K. Cheng, K.C. Rice, and K. Gawrisch Biophys. J. 96 2009 4916
18. A. Dyson, M. Peacock, A. Chen, J.P. Courade, M. Yaqoob, A. Groarke, C. Brain, Y. Loong, and A. Fox Pain 116 2005 129
19. X.H. Yu, C.Q. Cao, G. Martino, C. Puma, A. Morinville, S. St-Onge, E. Lessard, M.N. Perkins, and J.M.A. Laird Pain 151 2010 337
20. T. Kiyoi, J.M. Adam, J.K. Clark, K. Davies, A.M. Easson, D. Edwards, H. Feilden, R. Fields, S. Francis, F. Jeremiah, D. McArthur, A.J. Morrison, A. Prosser, P.D. Ratcliffe, J. Schulz, G. Wishart, J. Baker, R. Campbell, J.E. Cottney, M. Deehan, O. Epemolu, and L. Evans Bioorg. Med. Chem. Lett. 21 2011 1748
21. C.A. Lipinski Drug Discov. Today Technol. 1 2004 337
22. J. Mensch, J. Oyarzabal, C. Mackie, and P. Augustijns J. Pharm. Sci. 98 2009 4429
23. J. Kelder, M. Wagener, and M. Timmers J.H. Noordik, Cheminformatics Developments 2004 IOS Press USA 111
24. J. Kelder, P.D.J. Grootenhuis, D.M. Bayada, L.P.C. Delbressine, and J.-P. Ploemen Pharm. Res. 16 1999 1514
25. A. Doran, R.S. Obach, B.J. Smith, N.A. Hosea, S. Becker, E. Callegari, C. Chen, X. Chen, E. Choo, J. Cianfrogna, L.M. Cox, J.P. Gibbs, M.A. Gibbs, H. Hatch, C.E.C.A. Hop, I.N. Kasman, J. LaPerle, J.-H. Liu, X. Liu, M. Logman, D. Maclin, F.M. Nedza, F. Nelson, E. Olson, S. Rahematpura, D. Raunig, S. Rogers, K. Schmidt, D.K. Spracklin, M. Szewc, M. Troutman, E. Tseng, M. Tu, J.W. Van Deusen, K. Venkatakrishnan, G. Walens, E.Q. Wang, D. Wong, A.S. Yasgar, and C. Zhang Drug Metab. Disp. 33 2005 165
26. J.M. Adam, J. Cairns, W. Caulfield, P. Cowley, I. Cumming, M. Easson, D. Edwards, M. Ferguson, R. Goodwin, F. Jeremiah, T. Kiyoi, A. Mistry, E. Moir, R. Morphy, J. Tierney, M. York, J. Baker, J.E. Cottney, A.K. Houghton, P.J. Westwood, and G. Walker Med. Chem. Commun. 1 2010 54
27. T. Kiyoi, M. York, S. Francis, D. Edwards, G. Walker, A.K. Houghton, J.E. Cottney, J. Baker, and J.M. Adam Bioorg. Med. Chem. Lett. 20 2010 4918
28. E.M. Moir, K. Yoshiizumi, J. Cairns, P. Cowley, M. Ferguson, F. Jeremiah, T. Kiyoi, R. Morphy, J. Tierney, G. Wishart, M. York, J. Baker, J.E. Cottney, A.K. Houghton, P. McPhail, A. Osprey, G. Walker, and J.M. Adam Bioorg. Med. Chem. Lett. 20 2010 7327
29. A.J. Morrison, J.M. Adam, J.A. Baker, R.A. Campbell, J.K. Clark, J.E. Cottney, M. Deehan, A.-M. Easson, R. Fields, S. Francis, F. Jeremiah, N. Keddie, T. Kiyoi, D.R. McArthur, K. Meyer, P.D. Ratcliffe, J. Schulz, G. Wishart, and K. Yoshiizumi Bioorg. Med. Chem. Lett. 21 2011 506
30. P. Ratcliffe, J.M. Adam, J. Baker, R. Bursi, R. Campbell, J.K. Clark, J.E. Cottney, M. Deehan, A.-M. Easson, D. Ecker, D. Edwards, O. Epemolu, L. Evans, R. Fields, S. Francis, P. Harradine, F. Jeremiah, T. Kiyoi, D. McArthur, A. Morrison, P. Passier, J. Pick, P.G. Schnabel, J. Schulz, H. Steinbrede, G. Walker, P. Westwood, G. Wishart, and J. Udo de Haes Bioorg. Med. Chem. Lett. 21 2011 2541
31. Brain, C. T.; Dziadulewicz, E. K.; Hart, T. W. (Novartis Pharma GMBH) PCT Int. Appl. 2003, WO2003066603.
32. M.R. Price, G.L. Baillie, A. Thomas, L.A. Stevenson, M. Easson, R. Goodwin, A. McLean, L. McIntosh, G. Goodwin, G. Walker, P. Westwood, J. Marrs, F. Thomson, P. Cowley, A. Christopoulos, R.G. Pertwee, and R.A. Ross Mol. Pharmacol. 68 2005 1484
33. 6) δ 1.30-1.40 (4H, m), 2.10 (1H, m), 2.90 (2H, b), 3.11 (2H, b), 3.20 (2H, t), 3.30 (2H, b), 3.48 (2H, b), 3.83 (2H, d) 3.95 (2H, s), 4.17 (2H, s), 4.50 (2H, d), 7.25 (1H, t), 7.35 (1H, d), 7.67 (1H, s), 8.08 (1H, s), 8.08 (1H, d), 8.26 (1H, s), 10.30 (1H, b). EsIMS: m/z 475.1, 473.1 [M+H]+.
34. I. Martin Drug Discovery Today 9 2004 161
35. Determination of CSF concentration: Male Wistar BRL rats were surgically prepared with cisterna magna cannulae to allow CSF sampling. LBP1 was dosed orally at 24 mg/kg and both CSF (30 μL) and tail vein blood (200 μL) serial samples were taken. Satellite rats were also dosed to enable terminal brain samples to be taken as a time-course. Plasma, brain and CSF samples were analysed by LC-MS/MS and were quantified using standard curves prepared in suitable matrices. CSF: free plasma ratios were calculated using in vitro plasma protein binding data from a separate study (performed at 10 μM).
36. D.D. Shen, A.A. Artu, and K.K. Adkinson Adv. Drug Deliv. Rev. 2004 1825 56
37. S.M. Murphy, M. Palmer, M.F. Poole, L. Padegimas, K. Hunady, J. Danzig, S. Gill, R. Gill, A. Ting, B. Sherf, K. Brunden, and A. Stricker-Krongrad J. Pharmacol. Toxicol. Methods 54 2006 42
38. W.M. Westerink, J.C. Stevenson, A. Lauwers, G. Griffioen, G.J. Horbach, and W.G. Schoonen Mutat. Res. 676 2009 113
39. P. Honore Drug Dev. Res. 67 2006 302
40. S.K. Joshi, and P. Honore Expert Opin. Drug Discovery 14 2006 323
41. R.G. Pertwee Br. J. Pharmacol. 46 1972 753