Design, synthesis, and structure-activity relationships of a series of novel N-aryl-2-phenylcyclopropanecarboxamide that are potent and orally active orexin receptor antagonists

Bioorganic and Medicinal Chemistry

Volumn 22, Issue 21, 2014, Pages 6071-6088

  Yoshida, Yu ^a   Terauchi, Taro ^a   Naoe, Yoshimitsu ^a   Kazuta, Yuji ^a   Ozaki, Fumihiro ^a   Beuckmann, Carsten T ^a   Nakagawa, Makoto ^a   Suzuki, Michiyuki ^a   Kushida, Ikuo ^a   Takenaka, Osamu ^a   Ueno, Takashi ^a   Yonaga, Masahiro ^a  

^a EISAI CO LTD   (Japan)

Author keywords

Hypocretin; Insomnia; Orexin receptor antagonist; Sleep disorder

Indexed keywords

1 [2 (3,4 DIMETHOXYPHENOXYMETHYL) 2 PHENYLCYCLOPROPANECARBONYL] 1,2,3,4 TETRAHYDROQUINOLINE; 1 [2 (3,4 DIMETHOXYPHENOXYMETHYL) 2 PHENYLCYCLOPROPYL] 2 PHENYLETHAN 1 ONE; 2 (3 METHOXYPHENOXYMETHYL) 2 PHENYL N (PYRIDIN 2 YL)CYCLOPROPANE 1 CARBOXAMIDE; 2 (3,4 DIMETHOXYPHENOXYMETHYL) 2 PHENYL N (PYRIDIN 2 YL)CYCLOPROPANE 1 CARBOXAMIDE; 2 (3,4 DIMETHOXYPHENOXYMETHYL) 2 PHENYL N (PYRIDIN 3 YL)CYCLOPROPANE 1 CARBOXAMIDE; 2 (3,4 DIMETHOXYPHENOXYMETHYL) 2 PHENYL N (PYRIDIN 4 YL)CYCLOPROPANE 1 CARBOXAMIDE; 2 (3,4 DIMETHOXYPHENYL) 2 (PHENOXYMETHYL) N (PYRIDIN 2 YL)CYCLOPROPANE 1 CARBOXAMIDE; 2 (4 METHOXYPHENOXYMETHYL) 2 PHENYL N (PYRIDIN 2 YL)CYCLOPROPANE 1 CARBOXAMIDE; 2 (PHENOXYMETHYL) 2 PHENYL N (PYRIDIN 2 YL)CYCLOPROPANE 1 CARBOXAMIDE; 2 [((3,4 DIMETHOXYPHENOXY)METHYL) 2 PHENYLCYCLOPROPYL] 5 FLUORO 1H BENZIMIDAZOLE; 2 [3 METHOXY 4 (METHOXYMETHYL)PHENOXYMETHYL] 2 PHENYL N (PYRIDIN 2 YL)CYCLOPROPANE 1 CARBOXAMIDE; 2 [4 METHOXY 3 (METHOXYMETHYL)PHENOXYMETHYL] 2 PHENYL N (PYRIDIN 2 YL)CYCLOPROPANE 1 CARBOXAMIDE; ALMOREXANT; N (4 METHYL 1,3 THIAZOL 2 YL) 2 [(3,4 DIMETHOXYPHENYL)OXYMETHYL] 2 PHENYLCYCLOPROPANECARBOXAMIDE; N (5 CYANOPYRIDIN 2 YL) 2 [(3,4 DIMETHOXYPHENYL)OXYMETHYL] 2 PHENYLCYCLOPROPANECARBOXAMIDE; N (5 METHYL 1,2 OXAZOL 3 YL) 2 [(3,4 DIMETHOXYPHENYL)OXYMETHYL] 2 PHENYLCYCLOPROPANE 1 CARBOXAMIDE; N (5 METHYL 1,3 THIAZOL 2 YL) 2 [(3,4 DIMETHOXYPHENYL) OXYMETHYL] 2 PHENYLCYCLOPROPANECARBOXAMIDE; N ARYL 2 PHENYLCYCLOPROPANECARBOXAMIDE; N CYCLOHEXYL 2 [(3,4 DIMETHOXYPHENYL)OXYMETHYL] 2 PHENYLCYCLOPROPANECARBOXAMIDE; N METHYL N PHENYL 2 [(3,4 DIMETHOXYPHENYL)OXYMETHYL] 2 PHENYLCYCLOPROPANECARBOXAMIDE; N PHENYL 2 [(3,4 DIMETHOXYPHENYL)OXYMETHYL] 2 PHENYLCYCLOPROPANECARBOXAMIDE; N [(2 (3,4 DIMETHOXYPHENOXYMETHYL) 2 PHENYLCYCLOPROPYL)METHYL]ANILINE; OREXIN 1 RECEPTOR; OREXIN 2 RECEPTOR; RECEPTOR BLOCKING AGENT; SB 649868; SUVOREXANT; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZOLPIDEM; [2 (3,4 DIMETHOXYPHENOXYMETHYL) 2 PHENYLCYCLOPROPYL]PHENYLMETHANONE; CYCLOPROPANE DERIVATIVE; OREXIN RECEPTOR;

26-33A AND B; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; DRUG ANALYSIS; DRUG BLOOD LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG DESIGN; DRUG DETERMINATION; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; FEMALE; HYDROGEN BOND; IN VITRO STUDY; IN VIVO STUDY; LATENT PERIOD; MALE; MOUSE; NONHUMAN; NONREM SLEEP; PHYSICAL CHEMISTRY; PROTON NUCLEAR MAGNETIC RESONANCE; SLEEP INDUCTION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; HUMAN; METABOLISM; SLEEP; SLEEP INITIATION AND MAINTENANCE DISORDERS; SYNTHESIS;

ANIMALS; CYCLOPROPANES; DRUG DESIGN; HUMANS; MALE; MICE; MICE, INBRED C57BL; MODELS, MOLECULAR; OREXIN RECEPTORS; SLEEP; SLEEP INITIATION AND MAINTENANCE DISORDERS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84908459059     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2014.08.034     Document Type: Article

References (34)

1. 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.C. 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
2. 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 II, W.N. Frankel, A.N. Van Den Pol, F.E. Bloom, K.M. Gautvik, and J.G. Sutcliffe Proc. Natl. Acad. Sci. U.S.A. 95 1998 322
3. A.N. Van den Pol, X.-B. Gao, K. Obrietan, T.S. Kilduff, and A.B. Belousov J. Neurosci. 18 1998 7962
4. C.T. Beuckmann, and M. Yanagisawa J. Mol. Med. (Berl.) 80 2002 329
5. 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
6. 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
7. 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
8. T.C. Thannickal, R.Y. Moore, R. Nienhuis, L. Ramanathan, S. Gulyani, M. Aldrich, M. Cornford, and J.M. Siegel Neuron 27 2000 469
9. C. Peyron, J. Faraco, W. Rogers, B. Ripley, S. Overeem, Y. Charnay, S. Nevsimalova, M. Aldrich, D. Reynolds, R. Albin, R. Li, M. Hungs, M. Pedrazzoli, M. Padigaru, M. Kucherlapati, J. Fan, R. Maki, G.J. Lammers, C. Bouras, R. Kucherlapati, S. Nishino, and E. Mignot Nat. Med. 6 2000 991
10. S. Nishino Handb. Clin. Neurol. 99 2011 765
11. M.A. Akanmu, and K. Honda Brain Res. 1048 2005 138
12. 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 J. Pharmacol. Exp. Ther. 330 2009 142
13. B.A. Kummangal, D. Kumar, and H.N. Mallick Behav. Brain Res. 237 2013 59
14. M.A. Steiner, J. Gatfield, C. Brisbane-Roch, H. Dietrich, A. Treiber, F. Jenck, and C. Boss ChemMedChem 8 2013 898
15. P.J. Coleman, and J.J. Renger Expert Opin. Ther. Pat. 20 2010 307
16. M.J. Bingham, J. Cai, and M.R. Deehan Curr. Opin. Drug Discov. Dev. 9 2006 551
17. T. Sakurai Nat. Rev. Neurosci. 8 2007 171
18. K. Etori, C.Y. Saito, N. Tsujino, and T. Sakurai Front. Neurosci. 8 2014 8
19. C. Boss, C. Brisbare-Roch, and F. Jenck J. Med. Chem. 52 2009 891
20. A.J. Roecker, and P.J. Coleman Curr. Top. Med. Chem. 8 2008 977
21. J. Gatfield, C. Brisbare-Roch, F. Jenck, and C. Boss Chem. Med. Chem. 5 2010 1197
22. L.P. Stasi, R. Artusi, C. Bovino, B. Buzzi, L. Canciani, G. Caselli, F. Colace, P. Garofalo, S. Giambuzzi, P. Larger, O. Letari, S. Mandelli, L. Perugini, S. Pucci, M. Salvi, and P. Toro Bioorg. Med. Chem. Lett. 23 2013 2653
23. T. Fujimoto, J. Kunitomo, Y. Tomata, K. Nishiyama, M. Nakashima, M. Hirozane, S. Yoshikubo, K. Hirai, and S. Marui Bioorg. Med. Chem. Lett. 21 2011 6414
24. 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
25. P. Hoever, S. de Haas, J. Winkler, R.C. Schoemaker, E. Chiossi, J. van Gerven, and J. Dingemanse Clin. Pharmacol. Ther. (N.Y., NY, U.S.) 87 2010 593
26. P. Bettica, G. Nucci, C. Pyke, L. Squassante, S. Zamuner, E. Ratti, R. Gomeni, and R. Alexander J. Psychopharmacol. 26 2012 1058
27. 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
28. C.D. Cox, M.J. Breslin, D.B. Whitman, J.D. Schreier, G.B. McGaughey, 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, T. Prueksaritanont, W.B. Anderson, C. Tang, S. Roller, T.D. Cabalu, D. Cui, G.D. Hartman, S.D. Young, K.S. Koblan, C.J. Winrow, J.J. Renger, and P.J. Coleman J. Med. Chem. 53 2010 5320
29. S. Shuto, S. Ono, Y. Hase, N. Kamiyama, H. Takada, K. Yamashita, and A. Matsuda J. Org. Chem 61 1996 915
30. A.I. Pack, R.J. Galante, G. Maislin, J. Cater, D. Metaxas, S. Lu, L. Zhang, R. Von Smith, T. Kay, J. Lian, K. Svenson, and L.L. Peters Physiol. Genom. 28 2007 232
31. C.T. Beuckmann, C.M. Sinton, S.C. Williams, J.A. Richardson, R.E. Hammer, T. Sakurai, and M. Yanagisawa J. Neurosci. 24 2004 4469
32. H. Depoortere, B. Zivkovic, K.G. Lloyd, D.J. Sanger, G. Perrault, S.Z. Langer, and G. Bartholini J. Pharmacol. Exp. Ther. 237 1986 649
33. R. Winsky-Sommerer Eur. J. Neurosci. 29 2009 1779
34. T. Sugaya, T. Yoshiba, T. Kajima, and Y. Ishihama Yakugaku Zasshi 122 2002 237