Suvorexant

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Suvorexant
Systematic (IUPAC) name
[(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone
Clinical data
Pregnancy cat. ?
Legal statusInvestigational
Identifiers
CAS number1030377-33-3 N
ATC codeNone
PubChemCID 24965990
ChemSpider24662178 N
Chemical data
FormulaC23H23ClN6O2 
Mol. mass450.920 g/mol (free base)
 N (what is this?)  (verify)
 
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Suvorexant
Systematic (IUPAC) name
[(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone
Clinical data
Pregnancy cat. ?
Legal statusInvestigational
Identifiers
CAS number1030377-33-3 N
ATC codeNone
PubChemCID 24965990
ChemSpider24662178 N
Chemical data
FormulaC23H23ClN6O2 
Mol. mass450.920 g/mol (free base)
 N (what is this?)  (verify)

Suvorexant (MK-4305) is a dual orexin receptor antagonist in development by Merck & Co.[1][2][3] It is not currently approved for commercial use, but it has completed three Phase III trials.[4] Results look promising.[5] The recent FDA review showed that the drug is associated with increased somnolence the next day and users of higher doses had an increased rate of suicidal ideation.[6]

Suvorexant works by turning off wakefulness rather than by inducing sleep.[7]

Suvorexant looks set to reach the market, as the FDA's peripheral and central nervous system advisory committee reportedly agreed that the drug was generally safe and effective for treating sleep maintenance and latency. The current debate is over what dose should be recommended to patients.[8]

References[edit]

  1. ^ Cox, C. D.; Breslin, M. J.; Whitman, D. B.; Schreier, J. D.; McGaughey, G. B.; Bogusky, M. J.; Roecker, A. J.; Mercer, S. P.; Bednar, R. A.; Lemaire, W.; Bruno, J. G.; Reiss, D. R.; Harrell, C. M.; Murphy, K. L.; Garson, S. L.; Doran, S. M.; Prueksaritanont, T.; Anderson, W. B.; Tang, C.; Roller, S.; Cabalu, T. D.; Cui, D.; Hartman, G. D.; Young, S. D.; Koblan, K. S.; Winrow, C. J.; Renger, J. J.; Coleman, P. J. (2010). "Discovery of the Dual Orexin Receptor Antagonist [(7R)-4-(5-Chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the Treatment of Insomnia". Journal of Medicinal Chemistry 53 (14): 5320–5332. doi:10.1021/jm100541c. PMID 20565075.  edit
  2. ^ Baxter, C. A.; Cleator, E.; Brands, K. M. J.; Edwards, J. S.; Reamer, R. A.; Sheen, F. J.; Stewart, G. W.; Strotman, N. A.; Wallace, D. J. (2011). "The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder". Organic Process Research & Development 15 (2): 367–375. doi:10.1021/op1002853.  edit
  3. ^ Winrow, C. J.; Gotter, A. L.; Cox, C. D.; Doran, S. M.; Tannenbaum, P. L.; Breslin, M. J.; Garson, S. L.; Fox, S. V.; Harrell, C. M.; Stevens, J.; Reiss, D. R.; Cui, D.; Coleman, P. J.; Renger, J. J. (2011). "Promotion of Sleep by Suvorexant—A Novel Dual Orexin Receptor Antagonist". Journal of Neurogenetics 25 (1–2): 52–61. doi:10.3109/01677063.2011.566953. PMID 21473737.  edit
  4. ^ Three completed trials:
  5. ^ Mieda, M; Sakurai, T (2013 Feb). "Orexin (hypocretin) receptor agonists and antagonists for treatment of sleep disorders. Rationale for development and current status.". CNS drugs 27 (2): 83–90. PMID 23359095. 
  6. ^ http://www.usatoday.com/story/news/nation/2013/05/20/fda-merck-insomnia-drug/2326921/
  7. ^ Kahn, Howie (June 1, 2012). "Sleep Better". In Koerth-Baker, Maggie. 32 Innovations That Will Change Your Tomorrow. New York Times. Retrieved November 29, 2012. 
  8. ^ http://www.rttnews.com/2123549/fda-panel-backs-merck-insomnia-drug-suvorexant-but-at-lower-doses.aspx



Actelion's research team is targeting the G-Protein coupled receptors, OX1 and OX2, which mediate the actions of orexins.