Discovery of MK-3697: A selective orexin 2 receptor antagonist (2-SORA) for the treatment of insomnia

Bioorganic and Medicinal Chemistry Letters

Volumn 24, Issue 20, 2014, Pages 4884-4890

  Roecker, Anthony J ^a   Reger, Thomas S ^a   Mattern, M Christa ^a   Mercer, Swati P ^a   Bergman, Jeffrey M ^a   Schreier, John D ^a   Cube, Rowena V ^a   Cox, Christopher D ^a   Li, Dansu ^a   Lemaire, Wei ^a   Bruno, Joseph G ^a   Harrell, C Meacham ^a   Garson, Susan L ^a   Gotter, Anthony L ^a   Fox, Steven V ^a   Stevens, Joanne ^a   Tannenbaum, Pamela L ^a   Prueksaritanont, Thomayant ^a   Cabalu, Tamara D ^a   Cui, Donghui ^a   Stellabott, Joyce ^a   Hartman, George D ^a   Young, Steven D ^a   Winrow, Christopher J ^a   Renger, John J ^a   Coleman, Paul J ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

2 SORA; Antagonists; Insomnia; Neurotransmitters; Orexin receptors

Indexed keywords

MK-3697; OREXIN RECEPTOR; PYRIDINE DERIVATIVE; THIAZOLE DERIVATIVE;

ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOG; DOSE RESPONSE; DRUG DEVELOPMENT; HUMAN; MOUSE; RAT; SLEEP INITIATION AND MAINTENANCE DISORDERS; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ANIMALS; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; HUMANS; MICE; MOLECULAR STRUCTURE; OREXIN RECEPTORS; PYRIDINES; RATS; SLEEP INITIATION AND MAINTENANCE DISORDERS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

EID: 84908691596     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2014.08.041     Document Type: Article

References (50)

1. S. Passarella, and M.-T. Duong Am. J. Health-Syst. Pharm. 65 2008 927
2. L. Gershell Nat. Rev. Drug Disc. 5 2006 15
3. C.M. Morin, and R. Benca Lancet 379 2012 1129
4. M. Daley, C.M. Morin, M. LeBlanc, J.-P. Gregoire, and J. Savard Sleep 32 2009 55
5. L.A. Chilcott, and C.M. Shapiro PharmacoEconomics 10 1996 1
6. M.K. Stoller Eur. Psychiatry 12 1997 41s
7. D. Reimann, and M.L. Perlis Sleep Med. Rev. 13 2009 205
8. J.J. Renger Curr. Top. Med. Chem. 8 2008 937
9. (a) FDA Requests Label Change for All Sleep Disorder Drug Products. FDA News Release P07045, 2007; http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncement/2007/ucm108868.htm; (b) FDA Drug Safety Communication: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist). FDA News Release January 10, 2013; http://www.fda.gov/drugs/drugsafety/ucm334033.htm; (c) FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR. FDA News Release May 14, 2013; http://www.fda.gov/Drugs/DrugSafety/ucm352085.htm; R.H. Farkas, E.F. Unger, and R. Temple N. Eng. J. Med. 369 2013 689 (e) FDA requiring lower starting dose for sleep drug Lunesta. FDA News Release May 15, 2014; http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm397453.htm
10. For recent reviews focused on orexin medicinal chemistry and biology, see: A.L. Gotter, A.L. Webber, P.J. Coleman, J.J. Renger, and C.J. Winrow Pharmacol. Rev. 64 2012 389
11. A.L. Gotter, A.J. Roecker, R. Hargreaves, P.J. Coleman, C.J. Winrow, and J.J. Renger Progr. Brain Res. 198 2012 163
12. T.E. Scammell, and C.J. Winrow Annu. Rev. Pharmacol. Toxicol. 51 2011 243
13. T. Sakurai, and M. Mieda Trends Pharmacol. Sci. 32 2011 451
14. C. Ruoff, M. Cao, and C. Guilleminault Curr. Pharm. Des. 17 2011 1476
15. M.E. Carter, J.S. Borg, and L. de Lecea Curr. Opin. Pharmacol. 9 2009 39
16. L.-C. Chiou, H.-J. Lee, Y.-C. Ho, S.-P. Chen, Y.-Y. Liao, C.-H. Ma, P.-C. Fan, J.-L. Fuh, and S.-J. Wang Curr. Pharm. Des. 16 2010 3089
17. M. Cao, and C. Guilleminault Curr. Neurol. Neurosci. Rep. 11 2011 227
18. C.J. Winrow, and J.J. Renger Br. J. Pharmacol. 171 2014 283
19. S.D. Kuduk, C.J. Winrow, and P.J. Coleman Ann. Rep. Med. Chem. 48 2013 73
20. J. Gatfield, C. Brisbare-Roch, F. Jenck, and C. Boss ChemMedChem 20 2010 1539
21. M.A. Akanmu, and K. Honda Brain Res. 1048 2005 138
22. J.M. Bergman, A.J. Roecker, S.P. Mercer, R.A. Bednar, D.R. Reiss, R.W. Ransom, C.M. Harrell, D.J. Pettibone, W. Lemaire, K. Murphy, C. Li, T. Prueksaritanont, C.J. Winrow, J.J. Renger, K.S. Koblan, G.D. Hartman, and P.J. Coleman Bioorg. Med. Chem. Lett. 18 2008 1425
23. C. Brisbare-Roch, J. Dingemanse, R. Koberstein, P. Hoever, H. Aissaoui, S. Flores, C. Mueller, O. Nayler, J. van Gerven, S.L. de Haas, P. Hess, C. Qiu, S. Buchmann, M. Scherz, T. Weller, W. Fischli, M. Clozel, and F. Jenck Nat. Med. 13 2007 150
24. R. Di Fabio, A. Pellacani, S. Faedo, A. Roth, L. Piccoli, P. Gerrard, R.A. Porter, C.N. Johnson, K. Thewlis, D. Donati, L. Stasi, S. Spada, G. Stemp, D. Nash, C. Branch, L. Kindon, M. Massagrande, A. Poffe, S. Braggio, E. Chiarparin, C. Marchioro, E. Ratti, and M. Corsi Bioorg. Med. Chem. Lett. 21 2011 5562
25. C.D. Cox, M.J. Breslin, G.B. McGaughey, D.B. Whitman, J.D. Schreier, M.J. Bogusky, A.J. Roecker, S.P. Mercer, R.A. Bednar, W. Lemaire, J.G. Bruno, D.R. Reiss, C.M. Harrell, K.L. Murphy, S.L. Garson, S.M. Doran, K.S. Koblan, T. Prueksaritanont, W.B. Anderson, C. Tang, S. Roller, T.D. Cabalu, D. Cui, R.G. Ball, G.D. Hartman, C.J. Winrow, J.J. Renger, and P.J. Coleman J. Med. Chem. 53 2010 5320
26. P.J. Coleman, J.D. Schreier, C.D. Cox, M.J. Breslin, D.B. Whitman, M.J. Bogusky, G.B. McGaughey, R.A. Bednar, W. Lemaire, S.M. Doran, S.V. Fox, S.L. Garson, A.L. Gotter, C.M. Harrell, D.R. Reiss, T.D. Cabalu, D. Cui, T. Prueksaritanont, J. Stevens, P.L. Tannenbaum, R.G. Ball, J. Stellabott, S.D. Young, G.D. Hartman, C.J. Winrow, and J.J. Renger ChemMedChem 7 2012 415
27. J. Herring, E. Snyder, K. Budd, J. Hutzelmann, D. Snavely, K. Liu, C. Lines, T. Roth, and D. Michelson Neurology 79 2012 2265
28. P. Hoever, G. Dorffner, H. Benes, T. Penzel, H. Danker-Hopfe, M.J. Barbanoj, G. Pillar, B. Saletu, O. Polo, D. Kunz, J. Zeitlhofer, S. Berg, M. Partinen, C.L. Bassetti, B. Hogl, I.O. Ebrahim, E. Holsboer-Traschsler, H. Bengtsson, Y. Peker, U.-M. Hemmeter, E. Chiossi, G. Hajak, and J. Dingemanse Clin. Pharmacol. Ther. 91 2012 975
29. Suvorexant (Belsomra®) was approved by the FDA for the treatment of insomnia on August 13, 2014 during the revision period for this Letter; see http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm409950.htm.
30. D. Michelson, E. Snyder, E. Paradis, M. Chengan-Liu, J. Hutzelmann, J.K. Walsh, A.D. Krystal, R.M. Benca, M. Cohn, C. Lines, T. Roth, and W.J. Herring Lancet 13 2014 461
31. 1R antagonists, see: T.P. Lebold, P. Bonaventure, and B.T. Shireman Bioorg. Med. Chem. Lett. 23 2013 4761
32. For examples of orally bioavailable 2-SORAs, please see: T. Fujimoto, J. Kunitomo, Y. Tomata, K. Nishiyama, M. Nakashima, M. Hirozane, S.-I. Yohikubo, K. Hirai, and S. Marui Bioorg. Med. Chem. Lett. 21 2011 6414
33. C. Betschart, S. Hintermann, D. Behnke, S. Cotesta, M. Fendt, C.E. Gee, L.H. Jacobson, G. Laue, S. Ofner, V. Chaudhari, S. Badiger, C. Pandit, J. Wagner, and D. Hoyer J. Med. Chem. 56 2013 7590
34. R.M. Chemelli, J.T. Willie, C.M. Sinton, J.K. Elmquist, T. Scammell, C. Lee, J.A. Richardson, S.C. Williams, Y. Xiong, Y. Kisanuki, T.E. Fitch, M. Nakazato, R.E. Hammer, C.B. Saper, and M. Yanagisawa Cell 98 1999 437
35. J.T. Willie, R.M. Chemelli, C.M. Sinton, S. Tokita, S.C. Williams, Y.Y. Kisanuki, J.N. Marcus, C. Lee, J.K. Elmquist, K.A. Kohlmeier, C.S. Leonard, J.A. Richardson, R.E. Hammer, and M. Yanagisawa Neuron 38 2003 715
36. L. Lin, F. Faraco, R. Li, H. Kadotani, W. Rogers, X. Lin, X. Qiu, P.J. de Jong, S. Nishino, and E. Mignot Cell 98 1999 365
37. S. Morairty, F.G. Revel, P. Malherbe, J.-L. Moreau, D. Valladao, J.G. Wettstein, T.S. Kilduff, and E. Borroni PloS One 7 2012 e39131
38. C. Dugovic, J.E. Shelton, L.E. Aluisio, I.C. Fraser, X. Jiang, S.W. Sutton, P. Bonaventure, S. Yun, X. Li, B. Lord, C.A. Dvorak, N.I. Carruthers, and T.W. Lovenberg JPET 330 2009 142
39. A.J. Roecker, S.P. Mercer, J.D. Schreier, C.D. Cox, M.E. Fraley, J.T. Steen, W. Lemaire, J.G. Bruno, C.M. Harrell, S.L. Garson, A.L. Gotter, S.V. Fox, J. Stevens, P.L. Tannenbaum, T. Prueksaritanont, T.D. Cabalu, D. Cui, J. Stellabott, G.D. Hartman, S.D. Young, C.J. Winrow, J.J. Renger, and P.J. Coleman ChemMedChem 9 2014 312
40. S.P. Mercer, A.J. Roecker, S.L. Garson, D.R. Reiss, C.M. Harrell, K.L. Murphy, J.G. Bruno, R.A. Bednar, W. Lemaire, D. Cui, T.D. Cabalu, C. Tang, T. Prueksaritanont, G.D. Hartman, S.D. Young, C.J. Winrow, J.J. Renger, and P.J. Coleman Bioorg. Med. Chem. Lett. 23 2013 6620
41. A manuscript in preparation will describe additional pharmacological and clinical data for MK-1064; Gotter, A. L.; et al. Manuscript in preparation.
42. Coleman, P. J.; Mercer, S. P.; Reger, T. S.; Roecker, A. J. Tripyridyl Carboxamide Orexin Receptor Antagonists, US8349872
43. Bergman, J. M.; Coleman, P. J.; Mattern, M. C.; Mercer, S. P.; Reger, T. S.; Roecker, A. J. Isonicotinamide Orexin Receptor Antagonists, US8592457
44. Bergman, J. M.; Coleman, P. J.; Roecker, A. J.; Schreier, J. D. 2,5-Disubstituted Phenyl Carboxamide Orexin Receptor Antagonists, US8399494
45. Li, D.; Roecker, A. J. Isoxazolopyridine Orexin Receptor Antagonists, WO 2013062858
46. Mercer, S. P.; Roecker, A. J. Preparation of Pyrazinecarboxamides as Orexin Receptor Antagonists, WO 2010141275
47. Coleman, P. J.; Cox, C. D.; Mercer, S. P.; Roecker, A. J.; Schreier, J. D. Pyridazine Carboxamide Orexin Receptor Antagonists, WO 2010051238.
48. Z. Yan, and G.W. Caldwell Curr. Top. Med. Chem. 12 2012 1291
49. J.H. Hochman, M. Yamazaki, T. Ohe, and J.H. Lin Curr. Drug Metab. 3 2002 257
50. J.H. Lin, and M. Yamazaki Drug Metab. Rev. 35 2003 417