Vornorexant is a modern small-molecule active pharmaceutical ingredient belonging to the dual orexin receptor antagonist class. It is also known by its development codes ORN-0829 and TS-142. Vornorexant is chemically identified by the molecular formula C23H22FN7O2 and has a molecular weight of approximately 447.46 g/mol. Public chemical databases identify Vornorexant as a selective antagonist of the orexin OX1 and OX2 receptors.
Orexin signaling plays an important role in maintaining wakefulness and regulating the sleep-wake cycle. Vornorexant belongs to the dual orexin receptor antagonist, or DORA, class and acts at both OX1 and OX2 receptors. This pharmacological mechanism distinguishes Vornorexant from conventional sleep medicines that act through other central nervous system pathways.
Preclinical research identified Vornorexant as a potent dual OX1R/OX2R antagonist, and subsequent clinical development evaluated its role in insomnia. Research publications describe its pharmacological, metabolic and pharmacokinetic characteristics in preclinical species and humans.
Vornorexant has the molecular formula C23H22FN7O2 and a molecular weight of approximately 447.46 g/mol. PubChem identifies the compound under CID 137419776 and reports the IUPAC name as:
[(2S)-2-[[3-(5-fluoro-2-pyridinyl)pyrazol-1-yl]methyl]-1,3-oxazinan-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone.
The molecule contains one defined stereocenter, and FDA's Global Substance Registration System records its stereochemistry as absolute.
Vornorexant should be distinguished from Vornorexant hydrate, which contains one water molecule and has the molecular formula C23H24FN7O3 with a molecular weight of approximately 465.5 g/mol. PubChem separately identifies Vornorexant hydrate as a related substance.
Vornorexant has progressed through clinical development for insomnia and has subsequently received regulatory approval in Japan in its hydrate form. Japan's PMDA records approval of Vorzzz tablets containing vornorexant hydrate in 2.5 mg, 5 mg and 10 mg strengths in August 2025.
The Japanese approval followed clinical development that included Phase III studies in patients with insomnia. A randomized, placebo-controlled Phase III study enrolled 596 Japanese patients and evaluated 5 mg and 10 mg doses of Vornorexant compared with placebo. The study reported statistically significant improvements in subjective sleep latency for both Vornorexant dose groups compared with placebo.
For pharmaceutical development and commercial API applications, Vornorexant requires controlled manufacturing processes, validated analytical methods and appropriate impurity characterization. Identification testing can involve chromatographic and spectrometric techniques such as HPLC and LC-MS, while a complete pharmaceutical quality-control program may additionally evaluate assay, related substances, residual solvents, elemental impurities, water content and other applicable quality attributes.
Since publicly available sources do not establish a universal USP, BP or Ph. Eur. monograph specification for Vornorexant, individual acceptance criteria should be based on the applicable regulatory filing, validated analytical methods, manufacturing process and customer-specific quality requirements.
Vornorexant is reported as a solid material, with commercial chemical references describing the material as white to light yellow. Reported research-use chemical data indicate high solubility in DMSO, with solubility of ≥100 mg/mL under the stated test conditions. The same data indicate that the saturation point was not determined.
The compound's physicochemical profile is relevant to pharmaceutical formulation and analytical development. Solubility, particle characteristics, solid-state form, stability and impurity profile should be evaluated using appropriate validated methods for the intended API application.
Vornorexant API can be relevant to pharmaceutical companies, formulation developers, contract research organizations and research institutions working on sleep medicine and orexin receptor pharmacology. Its development and regulatory history make it an important API for pharmaceutical research and development involving modern dual orexin receptor antagonists.
For API procurement and development activities, technical documentation should include appropriate analytical information, batch-specific specifications, certificate of analysis, safety documentation and applicable regulatory information. The exact grade, solid form and specifications should be confirmed according to the intended pharmaceutical application.
Vornorexant API manufacturing and supply requires careful control of chemical synthesis, purification, analytical testing and quality assurance. A pharmaceutical API manufacturing program should operate under an appropriate quality management system and maintain traceability throughout raw-material qualification, production, testing, packaging and storage.
For pharmaceutical development, Vornorexant should be evaluated according to the applicable regulatory and customer requirements rather than relying solely on generic chemical supplier specifications. Analytical characterization and batch-release testing should be established based on the intended use and regulatory expectations.
Vornorexant represents a newer generation of orexin-targeting pharmaceutical ingredients and has progressed from discovery and preclinical development through human clinical studies and regulatory approval in Japan. Its chemical identity, dual orexin receptor mechanism and clinical development history make it a relevant API for pharmaceutical research and development in insomnia therapeutics.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |