Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant

Bioorganic and Medicinal Chemistry Letters

Volumn 25, Issue 3, 2015, Pages 444-450

  Raheem, Izzat T ^a   Breslin, Michael J ^a   Bruno, Joseph ^a   Cabalu, Tamara D ^a   Cooke, Andrew ^a   Cox, Christopher D ^a   Cui, Donghui ^a   Garson, Susan ^a   Gotter, Anthony L ^a   Fox, Steven V ^a   Harrell, C Meacham ^a   Kuduk, Scott D ^a   Lemaire, Wei ^a   Prueksaritanont, Thomayant ^a   Renger, John J ^a   Stump, Craig ^a   Tannenbaum, Pamela L ^a   Williams, Peter D ^a   Winrow, Christopher J ^a   Coleman, Paul J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Active wake; Delta sleep; Dual orexin receptor antagonist (DORA); Filorexant; REM sleep; Selective orexin receptor antagonist (SORA)

Indexed keywords

ALMOREXANT; CYTOCHROME P450 3A4; ETHER DERIVATIVE; FILOREXANT; HETEROCYCLIC COMPOUND; OREXIN 1 RECEPTOR; OREXIN 2 RECEPTOR; PE 6; PIPERIDINE DERIVATIVE; SB 649868; SUVOREXANT; UNCLASSIFIED DRUG; MK-6096; OREXIN RECEPTOR; PIPERIDINE; PROTEIN BINDING; PYRIMIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VIVO STUDY; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; NONREM SLEEP; PHASE 2 CLINICAL TRIAL (TOPIC); PHYSICAL CHEMISTRY; RAT; RECEPTOR OCCUPANCY; REM SLEEP; SIGNAL TRANSDUCTION; WAKEFULNESS; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DOG; DRUG EFFECTS; DRUG SCREENING; HALF LIFE TIME; HUMAN; METABOLISM; SLEEP; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

DORAS; PORZANA; RATTUS;

ANIMALS; DOGS; DRUG EVALUATION, PRECLINICAL; ETHERS; HALF-LIFE; HUMANS; OREXIN RECEPTORS; PIPERIDINES; PROTEIN BINDING; PYRIMIDINES; RATS; SLEEP; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84920716492     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2014.12.056     Document Type: Article

References (25)

1. L. de Lecea, T.S. Kilduff, C. Peyron, X.B. Gao, P.E. Foye, P.E. Danielson, C. Fukuhara, E.L.F. Battenberg, V.T. Gautvik, F.S. Bartlett, W.N. Frankel, A.N. van den Pol, F.E. Bloom, K.M. Gautvik, and J.G. Sutcliffe PNAS 95 1998 322
2. T. Sakurai, A. Amemiya, M. Ishii, I. Matsuzaki, R.M. Chemelli, H. Tanaka, S.C. Williams, J.A. Richardson, G.P. Kozlowski, S. Wilson, J.R.S. Arch, R.E. Buckingham, A.C. Haynes, S.A. Carr, R.S. Annan, D.E. McNulty, W.S. Liu, J.A. Terrett, N.A. Elshourbagy, D.J. Bergsma, and M. Yanagisawa Cell 92 1998 573
3. L. Lin, J. Faraco, R. Li, H. Kadotani, W. Rogers, X. Lin, X. Qiu, P.J. de Jong, S. Nishino, and E. Mignot Cell 98 1999 365
4. 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
5. T.C. Thannickal, R.Y. Moore, R. Nienhuis, S. Ramanathan, S. Gulyani, M. Aldrich, M. Cornford, and J.M. Siegel Neuron 27 2000 469
6. 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. Hartmann, C.J. Winrow, and J.J. Renger ChemMedChem 7 2012 415
7. 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
8. J. Gatfield, C. Brisbare-Roch, F. Jenck, and C. Boss ChemMedChem 5 2010 1197
9. T.P. Lebold, P. Bonaventure, and B.T. Shireman Bioorg. Med. Chem. Lett. 23 2013 4761
10. N. Tsujino, and T. Sakurai Pharmacol. Rev. 61 2009 162
11. A.L. Gotter, A.L. Webber, P.J. Coleman, J.J. Renger, and C.J. Winrow Pharmacol. Rev. 64 2012 389
12. K.A. Kohlmeier, C.J. Tyler, M. Kalogiannis, M. Ishibashi, M.P. Kristensen, I. Gumenchuk, R.M. Chemelli, Y.Y. Kisanuki, M. Yanagisawa, and C.S. Leonard Front. Neurosci. 7 2013 246
13. M. Mieda, E. Hasegawa, Y.Y. Kisanuki, C.M. Sinton, M. Yanagisawa, and T. Sakurai J. Neurosci. 31 2011 6518
14. 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 311
15. S.D. Kuduk, J.W. Skudlarek, C.N. DiMarco, J.G. Bruno, M.A. Pausch, J.A. O'Brien, T.D. Cabalu, J. Stevens, J. Brunner, P.L. Tannenbaum, A.L. Gotter, C.J. Winrow, J.J. Renger, and P.J. Coleman Bioorg. Med. Chem. Lett. 24 2014 1784
16. C.J. Winrow, A.L. Gotter, C.D. Cox, S.M. Doran, P.L. Tannenbaum, M.J. Breslin, S.L. Garson, S.V. Fox, C.M. Harrell, J. Stevens, D.R. Reiss, D. Cui, P.J. Coleman, and J.J. Renger J. Neurogenet. 25 2011 52
17. 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
18. Connor, K. M. A Dual Orexin Receptor Antagonist, MK-6096, in Patients with Primary Insomnia: Randomized, Controlled, Crossover Polysomnography Study. Presented at the World Sleep Congress, Kyoto, Japan, 2011. Talk# PO-1-236.
19. L.P.C. Nielsen, C.P. Stevenson, D.G. Blackmond, and E.N. Jacobsen J. Am. Chem. Soc. 126 2004 1360
20. I.A. O'Neil, E. Cleator, J.M. Southern, N. Hone, and D.J. Topolczay Synlett 2000 695
21. B.J. Margolis, K.A. Long, D.L.T. Laird, J.C. Ruble, and S.R. Pulley J. Org. Chem. 72 2007 2232
22. A.L. Gotter, C.J. Winrow, J. Brunner, S.L. Garson, S.V. Fox, J. Binns, C.M. Harrell, D. Cui, K.L. Yee, M. Stiteler, J. Stevens, A. Savitz, P.L. Tannenbaum, S.J. Tye, T. McDonald, L. Yao, S.D. Kuduk, J. Uslaner, P.J. Coleman, and J.J. Renger BMC Neurosci. 14 2013 1
23. C.J. Winrow, A.L. Gotter, C.D. Cox, P.L. Tannenbaum, S.L. Garson, S.M. Doran, M.J. Breslin, J.D. Schreier, S.V. Fox, C.M. Harrell, J. Stevens, D.R. Reiss, D. Cui, P.J. Coleman, and J.J. Renger Neuropharmacology 62 2012 978
24. Patent Application WO 2014/113303 A1, published July 24, 2014.
25. G. McGaughey, C.I. Bayly, C.D. Cox, J.D. Schreier, M.J. Breslin, M.J. Bogusky, S. Pitzenberger, R. Ball, and P.J. Coleman J. Comput. Aided Mol. Des. 28 2014 5