Vornorexant information

Vornorexant
Clinical data
Other names	ORN-0829; TS-142
Routes of; administration	By mouth
Drug class	Orexin antagonist
Pharmacokinetic data
Elimination half-life	1.3–3.3 hours
Identifiers
	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;
CAS Number	2265899-49-6;
PubChem CID	137419776;
ChemSpider	61751857;
UNII	ZY54BP1CK3;
Chemical and physical data
Formula	C23H22FN7O2
Molar mass	447.474 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=C(C=C1)N2N=CC=N2)C(=O)N3CCCO[C@H]3CN4C=CC(=N4)C5=NC=C(C=C5)F;
	InChI InChI=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; Key:AEZZJXJIJFSUEM-QFIPXVFZSA-N;

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.^[3]^[4]^[5] It is a dual orexin OX₁ and OX₂ receptor antagonist (DORA).^[5]^[6] The medication is taken by mouth.^[1] As of June 2021, vornorexant is in phase 2 clinical trials for insomnia and phase 1 trials for sleep apnea.^[3] It is under development by Taisho Pharmaceutical.^[3]

Vornorexant has a time to peak of 2.5 hours and a relatively short elimination half-life of 1.3 to 3.3 hours.^[1]^[2] It was designed to have a short half-life and duration in order to reduce next-day side effects like somnolence.^[5]

^ ^a ^b ^c ^d Uchiyama M, Kambe D, Imadera Y, Kajiyama Y, Ogo H, Uchimura N (July 2022). "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". Psychopharmacology. 239 (7): 2143–2154. doi:10.1007/s00213-022-06089-6. PMC 9205809. PMID 35296912.
^ ^a ^b Uchiyama M, Kambe D, Imadera Y, Sunaga H, Hasegawa S, Nogi T, Kajiyama Y, Yoshida S, Ogo H, Uchimura N (April 2020). "0146 Efficacy and Safety of Single Dose of TS-142, a Novel and Potent Dual Orexin Receptor Antagonist, in Insomnia Patients". Sleep. 43 (Supplement 1): A58. doi:10.1093/sleep/zsaa056.144. eISSN 1550-9109. ISSN 0161-8105.
^ ^a ^b ^c "TS 142 - AdisInsight".
^ Muehlan C, Vaillant C, Zenklusen I, Kraehenbuehl S, Dingemanse J (November 2020). "Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders". Expert Opinion on Drug Metabolism & Toxicology. 16 (11): 1063–1078. doi:10.1080/17425255.2020.1817380. PMID 32901578. S2CID 221572078.
^ ^a ^b ^c Jacobson LH, Hoyer D, de Lecea L (May 2022). "Hypocretins (orexins): The ultimate translational neuropeptides". Journal of Internal Medicine. 291 (5): 533–556. doi:10.1111/joim.13406. PMID 35043499. S2CID 248119793.
^ Futamura A, Suzuki R, Tamura Y, Kawamoto H, Ohmichi M, Hino N, et al. (July 2020). "Discovery of ORN0829, a potent dual orexin 1/2 receptor antagonist for the treatment of insomnia". Bioorganic & Medicinal Chemistry. 28 (13): 115489. doi:10.1016/j.bmc.2020.115489. PMID 32482533. S2CID 216517776.

[pmid35296912-1] Uchiyama M, Kambe D, Imadera Y, Kajiyama Y, Ogo H, Uchimura N (July 2022). "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". Psychopharmacology. 239 (7): 2143–2154. doi:10.1007/s00213-022-06089-6. PMC 9205809. PMID 35296912.

[UchiyamaKambeImadera2020-2] Uchiyama M, Kambe D, Imadera Y, Sunaga H, Hasegawa S, Nogi T, Kajiyama Y, Yoshida S, Ogo H, Uchimura N (April 2020). "0146 Efficacy and Safety of Single Dose of TS-142, a Novel and Potent Dual Orexin Receptor Antagonist, in Insomnia Patients". Sleep. 43 (Supplement 1): A58. doi:10.1093/sleep/zsaa056.144. eISSN 1550-9109. ISSN 0161-8105.

[AdisInsight-3] "TS 142 - AdisInsight".

[pmid32901578-4] Muehlan C, Vaillant C, Zenklusen I, Kraehenbuehl S, Dingemanse J (November 2020). "Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders". Expert Opinion on Drug Metabolism & Toxicology. 16 (11): 1063–1078. doi:10.1080/17425255.2020.1817380. PMID 32901578. S2CID 221572078.

[pmid35043499-5] Jacobson LH, Hoyer D, de Lecea L (May 2022). "Hypocretins (orexins): The ultimate translational neuropeptides". Journal of Internal Medicine. 291 (5): 533–556. doi:10.1111/joim.13406. PMID 35043499. S2CID 248119793.

[pmid32482533-6] Futamura A, Suzuki R, Tamura Y, Kawamoto H, Ohmichi M, Hino N, et al. (July 2020). "Discovery of ORN0829, a potent dual orexin 1/2 receptor antagonist for the treatment of insomnia". Bioorganic & Medicinal Chemistry. 28 (13): 115489. doi:10.1016/j.bmc.2020.115489. PMID 32482533. S2CID 216517776.

Vornorexant information

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Clinical data

Other names	ORN-0829; TS-142
Routes of administration	By mouth^[1]
Drug class	Orexin antagonist
Pharmacokinetic data
Elimination half-life	1.3–3.3 hours^[1]^[2]
Identifiers
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
CAS Number	2265899-49-6
PubChem CID	137419776
ChemSpider	61751857
UNII	ZY54BP1CK3
Chemical and physical data
Formula	C₂₃H₂₂FN₇O₂
Molar mass	447.474 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC1=CC(=C(C=C1)N2N=CC=N2)C(=O)N3CCCO[C@H]3CN4C=CC(=N4)C5=NC=C(C=C5)F
InChI InChI=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 Key:AEZZJXJIJFSUEM-QFIPXVFZSA-N