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Purity: ≥98%
5-R-Rivaroxaban is (R)-enantiomer of Rivaroxaban (also known as BAY 59-7939) which is the first orally available, direct inhibitor of Factor Xa with Ki and IC50 of 0.4 nM and 0.7 nM in cell-free assays, respectively. Rivaroxaban binds to the Tyr288 in S1 pocket of factor Xa through the interaction of Tyr288 and the chlorine substituent of the chlorothiophene moiety. Rivaroxabanis used as an oral anticoagulant developed by Bayer amd was marketed in a number of countries with the brand name of Xarelto. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs four hours after a dose. The effects lasts 8–12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible.
| Targets |
An oral direct Factor Xa (FXa) inhibitor called rivaroxaban (BAY 59-7939) is being developed for the treatment and prevention of venous and arterial thrombosis. Rivaroxaban inhibits prothrombinase activity (IC50 2.1 nM) and human FXa (Ki 0.4 nM) competitively with selectivity that is >10,000 times better than that of other serine proteases. In comparison to rat plasma (IC50 290 nM), human and rabbit plasma exhibit a more effective inhibition of endogenous FXa by rivaroxaban (IC50 21 nM). In human plasma, it exhibits anticoagulant properties, activating partial thromboplastin time at 0.69 μM and increasing prothrombin time (PT)[2].
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| ln Vitro |
An oral direct Factor Xa (FXa) inhibitor called rivaroxaban (BAY 59-7939) is being developed for the treatment and prevention of venous and arterial thrombosis. Rivaroxaban inhibits prothrombinase activity (IC50 2.1 nM) and human FXa (Ki 0.4 nM) competitively with selectivity that is >10,000 times better than that of other serine proteases. In comparison to rat plasma (IC50 290 nM), human and rabbit plasma exhibit a more effective inhibition of endogenous FXa by rivaroxaban (IC50 21 nM). In human plasma, it exhibits anticoagulant properties, activating partial thromboplastin time at 0.69 μM and increasing prothrombin time (PT)[2].
BAY 59-7939 competitively inhibited purified human FXa with a Ki of 0.4 nM and an IC₅₀ of 0.7 nM. It showed similar affinity for purified rabbit FXa (IC₅₀ 0.8 nM) but lower potency against rat FXa (IC₅₀ 3.4 nM). In plasma, it inhibited endogenous FXa activated by Russell's viper venom with IC₅₀ values of 21 nM (human and rabbit) and 290 nM (rat). It prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) in human, rabbit, and rat plasma in a concentration-dependent manner, with PT being more sensitive.[1] |
| ln Vivo |
A strong and specific direct FXa inhibitor with good oral absorption and in vivo action is rivaroxaban (BAY 59-7939)[1]. When given as an intravenous bolus prior to thrombus induction, rivaroxaban (BAY 59-7939) decreases thrombus formation (ED50 0.1 mg/kg), suppresses FXa, and dose-dependently prolongs PT. At the ED50, there is a small change in PT and FXa (1.8-fold increase and 32% inhibition, respectively). At a dosage of 0.3 mg/kg, which virtually completely blocks thrombus formation, rivaroxaban exhibits a moderate prolongation of PT (3.2±0.5-fold) and a suppression of FXa activity (65±3%)[2].
BAY 59-7939 demonstrated dose-dependent antithrombotic activity in animal models. In a rat venous stasis model (fibrin-rich thrombi), intravenous administration reduced thrombus formation with an ED₅₀ of 0.1 mg/kg. In rat and rabbit arteriovenous (AV) shunt models (fibrin- and platelet-rich thrombi), oral administration reduced thrombus formation with ED₅₀ values of 5.0 mg/kg and 0.6 mg/kg, respectively. At antithrombotic doses (3 mg/kg p.o.), it did not significantly prolong bleeding times in rats or rabbits.[1] |
| Enzyme Assay |
The inhibitory activity of BAY 59-7939 against purified serine proteases was measured using chromogenic or fluorogenic substrates in 96-well microtiter plates at 25°C.
Enzymes were pre-incubated with the compound or vehicle for 10 minutes, followed by substrate addition. Reaction progress was monitored spectrophotometrically or fluorometrically for up to 20 minutes. For FXa inhibition, human FXa (0.5 nM) was assayed in Tris-HCl buffer with BSA. The Ki was calculated using the Cheng-Prusoff equation.[1] The effect on prothrombinase activity was assessed by measuring thrombin generation. Human FXa was incubated with washed platelets, CaCl₂, and prothrombin. After 20 minutes, generated thrombin was quantified using a chromogenic substrate.[1] |
| Animal Protocol |
Dssolved in polyethylene glycol/H2O/ glycerol (996 g/100 g/60 g) (for i.v.); and dissolved in solutol/ethanol/H2O [40%/10%/50% (v/v/v)] (for p.o.); ≤0.3 mg/kg for both i.v. and for p.o.; i.v. injection or Oral gavageFasted, male Wistar rats (HsdCpb:WU) and fasted, female New Zealand White rabbits (Esd:NZW).
Rat Venous Stasis Model: Anesthetized male Wistar rats received BAY 59-7939 or vehicle intravenously 15 minutes before thrombus induction. Thromboplastin was injected, and the abdominal vena cava was ligated. Thrombi were removed and weighed 15 minutes later.[1] Rat and Rabbit AV Shunt Model: Anesthetized animals were cannulated to connect the carotid artery and jugular vein with a shunt containing a thrombogenic nylon thread. BAY 59-7939 or vehicle was administered orally 90 minutes before the shunt was opened for 15 minutes. The thrombus formed on the thread was weighed.[1] Rat Tail Bleeding Model: BAY 59-7939 or vehicle was given orally 90 minutes before transection of the rat tail tip. Bleeding time was measured until cessation of continuous blood flow.[1] Rabbit Ear Bleeding Model: Anesthetized rabbits received BAY 59-7939 or vehicle orally. Standardized incisions were made on the ear at 90 and 105 minutes post-dose, and bleeding time was recorded.[1] |
| ADME/Pharmacokinetics |
BAY 59-7939 has been reported to have high oral bioavailability (60-86%) in rats and dogs. In a rabbit arteriovenous shunt model, plasma concentrations at the effective antithrombotic dose (ED₅₀) were approximately 14 times lower than in a rat arteriovenous shunt model, which is related to differences in plasma IC₅₀ values of FXa inhibitors between different species. [1]
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| Toxicity/Toxicokinetics |
At the effective oral antithrombotic dose (3 mg/kg in the arteriovenous shunt model), BAY 59-7939 did not significantly prolong the tail bleeding time in rats or the ear bleeding time in rabbits. At higher oral doses (6 and 10 mg/kg in rats), a dose-dependent moderate prolongation of bleeding time was observed (approximately 2-fold and 3-fold, respectively). [1]
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| References |
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| Additional Infomation |
BAY 59-7939 is an oral, direct, reversible FXa inhibitor used for the prevention and treatment of arterial and venous thrombosis. It acts at the junction of intrinsic and extrinsic coagulation pathways, inhibiting thrombin burst generation. Its mechanism of action does not involve direct inhibition of platelet aggregation, but may indirectly reduce platelet activation by reducing thrombin generation. Based on its potency, selectivity, and efficacy demonstrated in preclinical models, as well as its favorable bleeding risk, it was selected for clinical development. [1]
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| Molecular Formula |
C19H18CLN3O5S
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| Molecular Weight |
435.88
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| Exact Mass |
435.065
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| CAS # |
865479-71-6
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| Related CAS # |
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| PubChem CID |
11524901
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
732.6±60.0 °C at 760 mmHg
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| Flash Point |
396.9±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.633
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| LogP |
1.84
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
645
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1COCC(=O)N1C2=CC=C(C=C2)N3C[C@H](OC3=O)CNC(=O)C4=CC=C(S4)Cl
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| InChi Key |
KGFYHTZWPPHNLQ-CQSZACIVSA-N
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| InChi Code |
InChI=1S/C19H18ClN3O5S/c20-16-6-5-15(29-16)18(25)21-9-14-10-23(19(26)28-14)13-3-1-12(2-4-13)22-7-8-27-11-17(22)24/h1-6,14H,7-11H2,(H,21,25)/t14-/m1/s1
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| Chemical Name |
5-chloro-N-[[(5R)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl]methyl]thiophene-2-carboxamide
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| Synonyms |
BAY 59-7939 R-enantiomer; BAY59-7939; BAY-59-7939 R-isomer; Rivaroxaban; 5-R-Rivaroxaban; 5R-Rivaroxaban; trade name: Xarelto.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 0.5% methylcellulose+0.2% Tween 80:5 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2942 mL | 11.4710 mL | 22.9421 mL | |
| 5 mM | 0.4588 mL | 2.2942 mL | 4.5884 mL | |
| 10 mM | 0.2294 mL | 1.1471 mL | 2.2942 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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