Rivaroxaban
[CAS 366789-02-8]

Identification

• Classification: API >> Blood system medication >> Anticoagulant and antiplatelet drugs
• Name: Rivaroxaban
• Synonyms: 5-Chloro-N-(((5S)-2-oxo-3-(4-(3-oxomorpholin-4-yl)phenyl)-1,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide
• Molecular Formula: C₁₉H₁₈ClN₃O₅S
• Molecular Weight: 435.88
• CAS Registry Number: 366789-02-8
• EC Number: 685-132-2
• SMILES: C1COCC(=O)N1C2=CC=C(C=C2)N3C[C@@H](OC3=O)CNC(=O)C4=CC=C(S4)Cl

Properties

• Density: 1.5$+/-$0.1 g/cm³ Calc.^*
• Boiling point: 732.6$+/-$60.0 $degree$C 760 mmHg (Calc.)^*
• Flash point: 396.9$+/-$32.9 $degree$C (Calc.)^*
• Solubility: DMSO 20 mg/mL, Water $lessThan$1 mg/mL (Expl.)
• Index of refraction: 1.633 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS09
• Risk Statements: H411
• Safety Statements: P273-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H332
Reproductive toxicity	Lact.	-	H362
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Specific target organ toxicity - single exposure	STOT SE	3	H335
Specific target organ toxicity - single exposure	STOT SE	2	H371
Skin sensitization	Skin Sens.	1B	H317
Respiratory sensitization	Resp. Sens.	1	H334
Specific target organ toxicity - single exposure	STOT SE	1	H370
Reproductive toxicity	Repr.	2	H361d
Reproductive toxicity	Repr.	1B	H360
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410

Discovery and Applications

Rivaroxaban is a synthetic small-molecule anticoagulant that functions as a direct, selective inhibitor of coagulation factor Xa. It is used clinically to prevent and treat thromboembolic disorders, including deep vein thrombosis, pulmonary embolism, and stroke prevention in patients with non-valvular atrial fibrillation. It represents one of the first orally active direct factor Xa inhibitors to reach widespread clinical use, marking a major shift away from vitamin K antagonists such as warfarin.

The discovery of rivaroxaban is part of a broader medicinal chemistry effort aimed at developing targeted anticoagulants that act at specific points in the coagulation cascade. Traditional anticoagulants interfere indirectly with clotting factor synthesis or function and often require monitoring due to variable pharmacokinetics and dietary interactions. In contrast, rivaroxaban was designed to directly inhibit a single activated enzyme in the coagulation pathway, factor Xa, which plays a central role in converting prothrombin to thrombin. By blocking this step, rivaroxaban reduces thrombin generation and subsequent fibrin clot formation.

Factor Xa is a serine protease located at a key junction in the coagulation cascade, where both intrinsic and extrinsic pathways converge. Because one molecule of factor Xa can generate a large amount of thrombin, it is considered an attractive target for anticoagulant therapy. Rivaroxaban binds directly to the active site of factor Xa in a reversible manner, preventing access of the natural substrate without requiring antithrombin as a cofactor. This distinguishes it from indirect inhibitors such as heparin.

From a structural perspective, rivaroxaban is a highly optimized heterocyclic compound containing multiple fused ring systems and functional groups arranged to interact precisely with the S1 and S4 binding pockets of factor Xa. The molecule contains a chlorothiophene moiety, an oxazolidinone-like core, and a morpholinone-linked side chain, which together contribute to both potency and selectivity. Hydrogen bonding, hydrophobic interactions, and shape complementarity all contribute to high-affinity binding within the enzyme active site.

A key feature of rivaroxaban’s molecular design is its balance between hydrophilic and lipophilic regions. This amphiphilic character supports oral bioavailability while maintaining sufficient solubility for systemic absorption. The compound is designed to be absorbed in the gastrointestinal tract and distributed systemically to reach circulating factor Xa. Its pharmacokinetic profile supports predictable anticoagulant effects without the need for routine coagulation monitoring in most patients.

The development of rivaroxaban involved extensive structure–activity relationship studies to optimize potency, selectivity, and pharmacokinetic properties. Early lead compounds targeting factor Xa were refined to improve oral bioavailability and reduce off-target effects. Crystallographic studies of factor Xa complexes played a significant role in guiding molecular design, enabling chemists to identify key binding interactions within the active site and adjacent specificity pockets.

Rivaroxaban is administered orally and undergoes partial hepatic metabolism, primarily involving cytochrome P450 enzymes such as CYP3A4 and CYP2J2, as well as non-CYP-mediated hydrolysis. A portion of the drug is excreted unchanged, while metabolites are eliminated via renal and fecal routes. This mixed elimination pathway contributes to its clinical use across a range of patient populations, although renal function must be considered in dosing decisions.

In clinical practice, rivaroxaban is widely used for both prophylactic and therapeutic anticoagulation. It is employed in the prevention of stroke and systemic embolism in patients with atrial fibrillation not caused by valvular disease, in the treatment of venous thromboembolism, and in the prevention of recurrent clot formation. Its predictable pharmacology and fixed-dose regimens have contributed to its adoption as an alternative to traditional anticoagulants.

The mechanism-based inhibition of factor Xa by rivaroxaban provides a targeted approach to anticoagulation with reduced variability compared with vitamin K antagonists. However, as with all anticoagulants, its use is associated with an increased risk of bleeding, which is an inherent consequence of inhibiting the coagulation cascade.

Overall, rivaroxaban is a direct, orally active factor Xa inhibitor that exerts its anticoagulant effect by selectively blocking the active site of a key serine protease in the coagulation pathway. Its significance lies in its rational structure-based design, predictable pharmacokinetics, and clinical role in the prevention and treatment of thromboembolic diseases, representing a major advancement in modern anticoagulant therapy.

References

2026. Patient Preferences in Anticoagulation Treatment: A Review of Discrete Choice Experiments. The Patient - Patient-Centered Outcomes Research.
DOI: 10.1007/s40271-025-00792-0

2026. [Acute venous disorders: deep vein thrombosis and superficial vein thrombosis of the lower extremity : Diagnosis and treatment in dermatology practice]. Dermatologie (Heidelberg, Germany).
PMID: 41758231