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Review

Orexin research: patent news from 2016

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Pages 1123-1133 | Received 16 Mar 2017, Accepted 15 Jun 2017, Published online: 28 Jun 2017

References

  • Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:1 page following 696.
  • de Lecea L, Kilduff TS, Peyron C, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95:322–327.
  • Boss C, Roch C. Recent trends in orexin research – 2010 to 2015. Bioorg Med Chem Lett. 2015;25:2875–2887.
  • Gotter AL, Webber AL, Coleman PJ, et al. International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin receptor function, nomenclature and pharmacology. Pharmacol Rev. 2012;64:389–420.
  • Gatfield J, Brisbare-Roch C, Jenck F, et al. Orexin receptor antagonists: a new concept in CNS disorders? ChemMedChem. 2010;5:1197–1214.
  • Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007;8:171–181.
  • Li SB, Giardino WJ, de Lecea L. Hypocretins and arousal. Curr Top Behav Neurosci. 2017;33:93–104.
  • Mahler SV, Moorman DE, Smith RJ, et al. Motivational activation: a unifying hypothesis of orexin/hypocretin function. Nat Neurosci. 2014;17:1298–1303.
  • Peyron C, Faraco J, Rogers W, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000;6:991–997.
  • Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. 2007;369:499–511.
  • Thannickal TC, Moore RY, Nienhuis R, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27:469–474.
  • James MH, Campbell EJ, Dayas CV. Role of the orexin/hypocretin system in stress-related psychiatric disorders. Curr Top Behav Neurosci. 2017;33:197–219.
  • Aston-Jones G, Smith RJ, Sartor GC, et al. Lateral hypothalamic orexin/hypocretin neurons: a role in reward-seeking and addiction. Brain Res. 2010;1314:74–90.
  • James MH, Mahler SV, Moorman DE, et al. A decade of orexin/hypocretin and addiction: where are we now? Curr Top Behav Neurosci. 2017;33:247–281.
  • So M, Hashimoto H, Saito R, et al. Inhibition of ghrelin-induced feeding in rats by pretreatment with a novel dual orexin receptor antagonist. J Physiol Sci. 2017.
  • Mahler SV, Smith RJ, Moorman DE, et al. Multiple roles for orexin/hypocretin in addiction. Prog Brain Res. 2012;198:79–121.
  • de Lecea L, Huerta R. Hypocretin (orexin) regulation of sleep-to-wake transitions. Front Pharmacol. 2014;5:16.
  • Kohlmeier KA, Tyler CJ, Kalogiannis M, et al. Differential actions of orexin receptors in brainstem cholinergic and monoaminergic neurons revealed by receptor knockouts: implications for orexinergic signaling in arousal and narcolepsy. Front Neurosci. 2013;7:246.
  • Alexandre D, Hautot C, Mehio M, et al. The orexin type 1 receptor is overexpressed in advanced prostate cancer with a neuroendocrine differentiation, and mediates apoptosis. Eur J Cancer. 2014;50:2126–2133.
  • Adamantidis AR, Zhang F, Aravanis AM, et al. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature. 2007;450:420–424.
  • Siegel JM, Boehmer LN. Narcolepsy and the hypocretin system – where motion meets emotion. Nat Clin Pract Neurol. 2006;2:548–556.
  • Boss C. Orexin receptor antagonists – a patent review (2010 to August 2014). Expert Opin Ther Pat. 2014;24:1367–1381.
  • Roecker AJ, Cox CD, Coleman PJ. Orexin receptor antagonists: new therapeutic agents for the treatment of insomnia. J Med Chem. 2016;59:504–530.
  • Heidmann B, Gatfield J, Roch C, et al. Discovery of highly potent dual orexin receptor antagonists via a scaffold-hopping approach. ChemMedChem. 2016;11:2132–2146.
  • Letavic MA, Bonaventure P, Carruthers NI, et al. Novel octahydropyrrolo[3,4-c]pyrroles are selective orexin-2 antagonists: SAR leading to a clinical candidate. J Med Chem. 2015;58:5620–5636.
  • Coleman PJ, Schreier JD, Cox CD, et al. Discovery of [(2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl][5-methyl-2 -(pyrimidin-2-yl)phenyl]methanone (MK-6096): a dual orexin receptor antagonist with potent sleep-promoting properties. ChemMedChem. 2012;7:415–24, 337.
  • Boss C, Roch-Brisbare C, Steiner MA, et al. Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: a potent, brain-penetrant dual orexin 1/orexin 2 receptor antagonist. ChemMedChem. 2014;9:2486–2496.
  • Roecker AJ, Mercer SP, Schreier JD, et al. Discovery of 5ʹ’-chloro-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2,2ʹ:5ʹ,3ʹ’-terpyridine-3ʹ-carbo xamide (MK-1064): a selective orexin 2 receptor antagonist (2-SORA) for the treatment of insomnia. ChemMedChem. 2014;9:311–322.
  • Bettica P, Squassante L, Zamuner S, et al. The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. Sleep. 2012;35:1097–1104.
  • Herring WJ, Snyder E, Budd K, et al. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012;79:2265–2274.
  • Hoever P, Dorffner G, Benes H, et al. Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial. Clin Pharmacol Ther. 2012;91:975–985.
  • Yoshida Y, Naoe Y, Terauchi T, et al. Discovery of (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluor opyridin-2-yl)cyclopropanecarboxamide (E2006): a potent and efficacious oral orexin receptor antagonist. J Med Chem. 2015;58:4648–4664.
  • Chemelli RM, Willie JT, Sinton CM, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999;98:437–451.
  • Lin L, Faraco J, Li R, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999;98:365–376.
  • Hasegawa E, Yanagisawa M, Sakurai T, et al. Orexin neurons suppress narcolepsy via 2 distinct efferent pathways. J Clin Invest. 2014;124:604–616.
  • Willie JT, Chemelli RM, Sinton CM, et al. Distinct narcolepsy syndromes in orexin receptor-2 and orexin null mice: molecular genetic dissection of non-REM and REM sleep regulatory processes. Neuron. 2003;38:715–730.
  • Brisbare-Roch C, Dingemanse J, Koberstein R, et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med. 2007;13:150–155.
  • Morairty SR, Revel FG, Malherbe P, et al. Dual hypocretin receptor antagonism is more effective for sleep promotion than antagonism of either receptor alone. Plos One. 2012;7:e39131.
  • Smith MI, Piper DC, Duxon MS, et al. Evidence implicating a role for orexin-1 receptor modulation of paradoxical sleep in the rat. Neurosci Lett. 2003;341:256–258.
  • Bonaventure P, Yun S, Johnson PL, et al. A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal without hypnotic effects. J Pharmacol Exp Ther. 2015;352:590–601.
  • Dugovic C, Shelton JE, Aluisio LE, et al. Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat. J Pharmacol Exp Ther. 2009;330:142–151.
  • Steiner MA, Gatfield J, Brisbare-Roch C, et al. Discovery and characterization of ACT-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist. ChemMedChem. 2013;8:898–903.
  • Gotter AL, Forman MS, Harrell CM, et al. Orexin 2 receptor antagonism is sufficient to promote NREM and REM sleep from mouse to man. Sci Rep. 2016;6:27147.
  • Kukkonen JP, Leonard CS. Orexin/hypocretin receptor signalling cascades. Br J Pharmacol. 2014;171:314–331.
  • Leonard CS, Kukkonen JP. Orexin/hypocretin receptor signalling: a functional perspective. Br J Pharmacol. 2014;171:294–313.
  • Kuduk SD, Liverton N, Luo Y Merck Sharp & Dhome Corp. WO 2016/101118, 2016
  • Liverton N, Kuduk SD, Beshore DC, et al. Merck Sharp & Dhome Corp. WO 2016/101119, 2016
  • Kuduk SD, Liverton N, Reger TS, et al. Merck Sharp & Dohme Corp. WO 2016/100162, 2016
  • Kim R, Kuduk SD, Liverton N, et al. Merck Sharp and Dohme Corp. WO 2016/100161, 2016
  • Kim R, Kuduk SD, Liverton N, et al. Merck Sharp & Dohme Corp. WO 2016/100157, 2016
  • Kuduk SD, Liverton N, Luo Y Merck Sharp & Dohme Corp. WO 2016/100156, 2016
  • Aissaoui H, Boss C, Brotschi C, et al. Actelion Pharmaceuticals Ltd. WO 2010/044054, 2010
  • Kuduk SD, Liverton N, Luo Y, et al. Merck Sharp & Dohme Corp. WO 2016/100154, 2016
  • Kuduk SD, Liverton N, Luo Y Merck Sharp & Dhome Corp. WO 2016/086357, 2016
  • Kuduk SD, Liverton N, Luo Y Merck Sharp & Dohme Corp. WO 2016/065583, 2016
  • Kuduk SD, Liverton N, Luo Y Merck Sharp & Dohme Corp. WO 2016/089722, 2016
  • Kuduk SD, Reger TS, Roecker AJ. Merck Sharp & Dohme Corp. WO 2016/085783, 2016
  • Kuduk SD, Reger TS, Skudlarek JW. Merck Sharp & Dohme Corp. WO 2016/085784, 2016
  • Wacker D, Roth BL. An alerting structure: human orexin receptor 1. Nat Struct Mol Biol. 2016;23:265–266.
  • Yin J, Babaoglu K, Brautigam CA, et al. Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptors. Nat Struct Mol Biol. 2016;23:293–299.
  • Yin J, Rosenbaum DM. The human orexin/hypocretin receptor crystal structures. Curr Top Behav Neurosci. 2016;33:1–15.
  • Liverton N, Kuduk SD, Beshore D, et al. Merck Sharp & Dohme Corp. WO 2016/065585, 2016
  • Liverton N, Kuduk SD, Beshore D, et al. Merck Sharp & dohme corp. Wo. 2016/065586. 2016.
  • Liverton N, Kuduk SD, Luo Y, et al. Merck Sharp & Dohme Corp. WO 2016/065584, 2016
  • Liverton N, Kuduk SD, Luo Y Merck Sharp & Dohme Corp. WO 2016/065587, 2016
  • Lebold TP, Dvorak CA, Coate HR, et al. Janssen Pharmaceutica NV. WO 2016/040789, 2016
  • Coate HR, Dvorak CA, Lebold TP, et al. Janssen Pharmaceutica NV. US 2016/0376280, 2016.
  • Hotta D, Sakurada I Mochida Pharmaceutical Co. Ltd. WO 2016/088813, 2016
  • Hotta D, Sakurada I, Ogawa K, et al. Mochida Pharmaceutical Co. Ltd. WO 2016/084866, 2016
  • Kamenecka TM, He Y-J Eolas Therapeutics Inc. WO 2016/025669, 2016
  • Knust H, Nettekoven M, Pinnard E, et al. F. Hoffmann-La Roche AG. WO 2010/012620, 2010
  • Kamei T, Arikawa Y, Ohashi T, et al. Takeda Pharmaceutical Company Limited. WO 2016/171248, 2016
  • Jin C, Liu Q, Zhang Y, et al. Sunshine Lake Pharma Co. Ltd. CN 105949203 2016 .
  • Zhang Y, Jin C, Gao J, et al. Sunshine Lake Pharma Co Ltd. WO 2017/012502, 2017
  • Nagase H, Yamamoto N, Yata M, et al. Design and synthesis of potent and highly selective orexin 1 receptor antagonists with a morphinan skeleton and their pharmacologies. J Med Chem. 2017;60:1018–1040.
  • Stump CA, Cooke AJ, Bruno J, et al. Discovery of highly potent and selective orexin 1 receptor antagonists (1-SORAs) suitable for in vivo interrogation of orexin 1 receptor pharmacology. Bioorg Med Chem Lett. 2016;26:5809–5814.
  • Wu S, Sun Y, Hu Y, et al. Discovery of novel substituted octahydropyrrolo[3,4-c]pyrroles as dual orexin receptor antagonists for insomnia treatment. Bioorg Med Chem Lett. 2017;27:1458–1462.
  • Nagahara T, Saitoh T, Kutsumura N, et al. Design and synthesis of non-peptide, selective orexin receptor 2 agonists. J Med Chem. 2015;58:7931–7937.
  • Heifetz A, Bodkin MJ, Biggin PC. Discovery of the first selective, nonpeptidic orexin 2 receptor agonists. J Med Chem. 2015;58:7928–7930.
  • Nagase H, Nagahara T University of Tsukuba. WO 2015/088000, 2015
  • Yanagisawa M, Nagase H, Saitoh T, et al. University of Tsukuba and Board of Regents, The University of Texas. WO 2016/133160, 2016
  • Nagase H, Yanagisawa M, Saitoh T, et al. University of Tsukuba and Board of Regents, The University of Texas System. WO 2016/199906, 2016
  • Turku A, Borrel A, Leino TO, et al. Pharmacophore model to discover OX1 and OX2 orexin receptor ligands. J Med Chem. 2016;59:8263–8275.
  • Dosa PI, Amin EA. Tactical approaches to interconverting GPCR agonists and antagonists. J Med Chem. 2016;59:810–840.
  • Voisin T, El Firar A, Fasseu M, et al. Aberrant expression of OX1 receptors for orexins in colon cancers and liver metastases: an openable gate to apoptosis. Cancer Res. 2011;71:3341–3351.
  • Couvineau A, Voisin T, Robert B, et al. INSERM, University Paris Diderot, University of Montpellier. WO 2016/113351, 2016
  • Robert B, Couvineau A, Martineau P INSERM, University of Montpellier, University Paris Diderot. WO 2016/135066, 2016
  • Couvineau A, Voisin T, Nicole P, et al. INSERM, University Paris Diderot, University of Montpellier. WO 2016/113356, 2016
  • Yin J, Mobarec JC, Kolb P, et al. Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant. Nature. 2015;519:247–250.

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