Vornorexant

{{Short description|Chemical compound}}

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| IUPAC_name = [(2S)-2-[[3-(5-fluoropyridin-2-yl)pyrazol-1-yl]methyl]-1,3-oxazinan-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone

| image = Vornorexant skeletal.svg

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| routes_of_administration = By mouth

| class = Orexin antagonist

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| elimination_half-life = 1.3–3.3 hours

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| CAS_number = 2265899-49-6

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| PubChem = 137419776

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| ChemSpiderID = 61751857

| UNII = ZY54BP1CK3

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| synonyms = ORN-0829; TS-142

| C=23 | H=22 | F=1 | N=7 | O=2

| SMILES = CC1=CC(=C(C=C1)N2N=CC=N2)C(=O)N3CCCO[C@H]3CN4C=CC(=N4)C5=NC=C(C=C5)F

| StdInChI_Ref =

| StdInChI = 1S/C23H22FN7O2/c1-16-3-6-21(31-26-8-9-27-31)18(13-16)23(32)30-10-2-12-33-22(30)15-29-11-7-20(28-29)19-5-4-17(24)14-25-19/h3-9,11,13-14,22H,2,10,12,15H2,1H3/t22-/m0/s1

| StdInChIKey_Ref =

| StdInChIKey = AEZZJXJIJFSUEM-QFIPXVFZSA-N

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Vornorexant, also known by its developmental code names ORN-0829 and TS-142, is an orexin antagonist medication which is under development for the treatment of insomnia and sleep apnea.{{Cite web|url=https://adisinsight.springer.com/drugs/800049420|title=TS 142 - AdisInsight}}{{cite journal | vauthors = Muehlan C, Vaillant C, Zenklusen I, Kraehenbuehl S, Dingemanse J | title = Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 16 | issue = 11 | pages = 1063–1078 | date = November 2020 | pmid = 32901578 | doi = 10.1080/17425255.2020.1817380 | s2cid = 221572078 }}{{cite journal | vauthors = Jacobson LH, Hoyer D, de Lecea L | title = Hypocretins (orexins): The ultimate translational neuropeptides | journal = Journal of Internal Medicine | volume = 291 | issue = 5 | pages = 533–556 | date = May 2022 | pmid = 35043499 | doi = 10.1111/joim.13406 | s2cid = 248119793 }} It is a dual orexin OX₁ and OX₂ receptor antagonist (DORA).{{cite journal | vauthors = Futamura A, Suzuki R, Tamura Y, Kawamoto H, Ohmichi M, Hino N, Tokumaru Y, Kirinuki S, Hiyoshi T, Aoki T, Kambe D, Nozawa D | display-authors = 6 | title = Discovery of ORN0829, a potent dual orexin 1/2 receptor antagonist for the treatment of insomnia | journal = Bioorganic & Medicinal Chemistry | volume = 28 | issue = 13 | pages = 115489 | date = July 2020 | pmid = 32482533 | doi = 10.1016/j.bmc.2020.115489 | s2cid = 216517776 }} The medication is taken by mouth.{{cite journal | vauthors = Uchiyama M, Kambe D, Imadera Y, Kajiyama Y, Ogo H, Uchimura N | title = Effects of TS-142, a novel dual orexin receptor antagonist, on sleep in patients with insomnia: a randomized, double-blind, placebo-controlled phase 2 study | journal = Psychopharmacology | volume = 239 | issue = 7 | pages = 2143–2154 | date = July 2022 | pmid = 35296912 | doi = 10.1007/s00213-022-06089-6 | doi-access = free | pmc = 9205809 }} As of June 2021, vornorexant is in phase 2 clinical trials for insomnia and phase 1 trials for sleep apnea. It is under development by Taisho Pharmaceutical.

Vornorexant has a time to peak of 2.5{{nbsp}}hours and a relatively short elimination half-life of 1.3 to 3.3{{nbsp}}hours.{{cite journal | vauthors = Uchiyama M, Kambe D, Imadera Y, Sunaga H, Hasegawa S, Nogi T, Kajiyama Y, Yoshida S, Ogo H, Uchimura N | title = 0146 Efficacy and Safety of Single Dose of TS-142, a Novel and Potent Dual Orexin Receptor Antagonist, in Insomnia Patients | journal = Sleep | date = April 2020 | volume = 43 | issue = Supplement 1 | pages = A58 | issn = 0161-8105 | eissn = 1550-9109 | doi = 10.1093/sleep/zsaa056.144 | pmid = | url = | doi-access = free }} It was designed to have a short half-life and duration in order to reduce next-day side effects like somnolence.