Edoxaban p-toluenesulfonate monohydrate
[CAS# 1229194-11-9]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism >> Factor Xa inhibitor
• Name: Edoxaban p-toluenesulfonate monohydrate
• Synonyms: N-(5-Chloropyridin-2-yl)-N'-((1S,2R,4S)-4-[(dimethyl amino)carbonyl]-2-[[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino]cyclohexyl)ethanediamide p-toluenesulfonate monohydrate
• Molecular Formula: C₂₄H₃₀ClN₇O₄S.C₇H₈O₃S.H₂O
• Molecular Weight: 738.28
• CAS Registry Number: 1229194-11-9
• EC Number: 991-362-7
• SMILES: CC1=CC=C(C=C1)S(=O)(=O)O.CN1CCC2=C(C1)SC(=N2)C(=O)N[C@@H]3C[C@H](CC[C@@H]3NC(=O)C(=O)NC4=NC=C(C=C4)Cl)C(=O)N(C)C.O

Properties

• Solubility: 7.2 mg/mL (DMSO) (Expl.)

Safety Data

• Hazard Symbols: GHS08 Warning
• Risk Statements: H373
• Safety Statements: P260-P319-P501

Discovery and Applications

Edoxaban p-toluenesulfonate monohydrate is a chemical compound that plays a crucial role in the field of anticoagulation therapy. It is the p-toluenesulfonate salt form of edoxaban, a direct oral anticoagulant (DOAC) that inhibits factor Xa in the coagulation cascade, thereby preventing blood clot formation. The chemical structure of edoxaban includes a heterocyclic scaffold with a series of functional groups that enable its interaction with the active site of factor Xa, a key enzyme in blood clotting. The addition of p-toluenesulfonate as a counterion in the monohydrate form helps to improve the solubility and stability of the compound.

The discovery of edoxaban dates back to the early 2000s, as part of ongoing efforts to develop more effective and safer anticoagulants. Traditional anticoagulants such as warfarin have been widely used for decades, but they require frequent monitoring and have many dietary and drug interactions. In contrast, DOACs like edoxaban offer the advantage of a fixed dosing regimen without the need for routine coagulation monitoring, making them more convenient for long-term use. Edoxaban’s specific mechanism of action, through the selective inhibition of factor Xa, contributes to its efficacy in preventing venous thromboembolism (VTE), stroke, and systemic embolism, especially in patients with atrial fibrillation.

The clinical application of edoxaban p-toluenesulfonate monohydrate is most notable in its role as a treatment for various thrombotic disorders. It is approved for use in patients with non-valvular atrial fibrillation to reduce the risk of stroke and systemic embolism. Additionally, edoxaban is used in the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as in the prevention of recurrent VTE after initial treatment. Its oral administration makes it an appealing alternative to injectable anticoagulants, providing ease of use and improved patient compliance.

One of the key advantages of edoxaban over older anticoagulants is its favorable pharmacokinetic profile. It has a predictable dose-response relationship, a relatively short half-life, and is primarily eliminated via renal excretion. This allows for a more straightforward dosing regimen, reducing the risk of bleeding associated with over-anticoagulation, which can occur with warfarin. However, like all anticoagulants, edoxaban carries a risk of bleeding, and patients on edoxaban are monitored for any signs of hemorrhagic complications.

Research is ongoing to further understand the optimal use of edoxaban in various patient populations. Clinical studies continue to explore its potential in preventing thromboembolic events in those undergoing major surgeries, as well as its application in special populations such as the elderly, patients with renal impairment, and those with cancer-associated thrombosis. There is also ongoing work to develop antidotes or reversal agents for edoxaban, which would further enhance its safety profile in emergency situations.

Overall, edoxaban p-toluenesulfonate monohydrate is a critical development in the field of anticoagulation therapy. Its discovery and application represent significant progress in the management of thrombotic disorders, offering an alternative to older anticoagulants with a more convenient and predictable dosing regimen. As research continues, edoxaban’s role in the treatment and prevention of thromboembolic events will likely expand, offering improved outcomes for patients in need of anticoagulation therapy.

References

2008. DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles. Journal of thrombosis and haemostasis : JTH.
DOI: 10.1111/j.1538-7836.2008.03064.x

2011. Edoxaban Tosylate. American journal of cardiovascular drugs : drugs, devices, and other interventions.
DOI: 10.2165/11533660-000000000-00000

2024. Perioperative Management of Patients Taking Direct Oral Anticoagulants: A Review. JAMA.
DOI: 10.1001/jama.2024.12708