Firazorexton Explained

Width:225px
Cas Number:2274802-95-6
Unii:U9MOX60GHD
Pubchem:137460733
Chemspiderid:115009503
Synonyms:TAK-994
Iupac Name:N-[(2''S'',3''S'')-2-[[3-(3,5-difluorophenyl)-2-fluorophenyl]methyl]-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]methanesulfonamide
C:22
H:25
F:3
N:2
O:4
S:1
Smiles:CC(C)(C(=O)N1CC[C@@H]([C@@H]1CC2=C(C(=CC=C2)C3=CC(=CC(=C3)F)F)F)NS(=O)(=O)C)O
Stdinchi:1S/C22H25F3N2O4S/c1-22(2,29)21(28)27-8-7-18(26-32(3,30)31)19(27)11-13-5-4-6-17(20(13)25)14-9-15(23)12-16(24)10-14/h4-6,9-10,12,18-19,26,29H,7-8,11H2,1-3H3/t18-,19-/m0/s1
Stdinchikey:VOSAWOSMGPKQEQ-OALUTQOASA-N

Firazorexton (; development code TAK-994) is an experimental orexin 2 (OX2) receptor agonist first described in a 2019 patent filed by Takeda Pharmaceutical Company.[1]

Firazorexton was studied by Takeda for the treatment of narcolepsy.[2] [3] It is a small-molecule and orally active compound and acts as a highly selective agonist of the orexin receptor 2 (OX2) with >700-fold selectivity over the orexin receptor 1 (OX1).[4] [5] [6] Firazorexton is related to danavorexton (TAK-925). The compound reached phase 2 clinical trials for narcolepsy. However, clinical development was discontinued in October 2021 for safety reasons.[7] [8] [9] [10] [11]

See also

Notes and References

  1. International Nonproprietary Names for Pharmaceutical Substances (INN) . WHO Drug Information . 34 . 1 . 2020 . 93–269 . Proposed INN: List 123 .
  2. Ishikawa T, Suzuki M, Kimura H . 0141 A Novel, Orally Available Orexin 2 Receptor-Selective Agonist, TAK-994, Shows Wake-Promoting Effects Following Chronic Dosing in an Orexin-Deficient Narcolepsy Mouse Model . Sleep . April 2020 . 43 . Supplement 1 . A56 . 0161-8105 . 1550-9109 . 10.1093/sleep/zsaa056.139 . free .
  3. Ishikawa T, Hara H, Kawano A, Tohyama K, Kajita Y, Miyanohana Y, Koike T, Kimura H . 6 . TAK-994, a Novel Orally Available Brain-Penetrant Orexin 2 Receptor-Selective Agonist, Suppresses Fragmentation of Wakefulness and Cataplexy-Like Episodes in Mouse Models of Narcolepsy . The Journal of Pharmacology and Experimental Therapeutics . 385 . 3 . 193–204 . June 2023 . 37001988 . 10.1124/jpet.122.001449 . 257879743 . free .
  4. Thorpy MJ . Recently Approved and Upcoming Treatments for Narcolepsy . CNS Drugs . 34 . 1 . 9–27 . January 2020 . 31953791 . 6982634 . 10.1007/s40263-019-00689-1 .
  5. Zhang D, Perrey DA, Decker AM, Langston TL, Mavanji V, Harris DL, Kotz CM, Zhang Y . 6 . Discovery of Arylsulfonamides as Dual Orexin Receptor Agonists . Journal of Medicinal Chemistry . 64 . 12 . 8806–8825 . June 2021 . 34101446 . 8994207 . 10.1021/acs.jmedchem.1c00841 .
  6. Pellitteri G, de Biase S, Valente M, Gigli GL . How treatable is narcolepsy with current pharmacotherapy and what does the future hold? . Expert Opinion on Pharmacotherapy . 22 . 12 . 1517–1520 . August 2021 . 33882765 . 10.1080/14656566.2021.1915987 . 233349300 .
  7. Jacobson LH, Hoyer D, de Lecea L . Hypocretins (orexins): The ultimate translational neuropeptides . Journal of Internal Medicine . 291 . 5 . 533–556 . May 2022 . 35043499 . 10.1111/joim.13406 . 248119793 .
  8. Web site: Takeda Provides Update on TAK-994 Clinical Program . Business Wire . 5 October 2021 .
  9. Web site: Takeda pauses TAK-994 clinical studies due to safety glitch . 6 October 2021 . The Pharma Letter .
  10. Web site: Jackson M . Scrip . Informa Pharma Intelligence . Takeda Halts Phase II Studies For Key R&D Asset TAK-994 In Narcolepsy . 6 October 2021 .
  11. Web site: Tong A . 6 October 2021 . Endpoints News . Takeda flashes red light on 'breakthrough' narcolepsy drug after PhII trials turned up mysterious safety signal .

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