480449-70-5

Basic information

• Product Name: edoxaban
• Synonyms: edoxaban;N-(5-Chloro-2-pyridinyl)-N'-[(1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-[[(4,5,6,7-tetrahydro-5-methylthiazolo[5,4-c]pyridin-2-yl)carbonyl]amino]cyclohexyl]ethanediamide;EthanediaMide, N1-(5-chlo...;EthanediaMide, N1-(5-chloro-2-pyridinyl)-N2-[(1S,2R,4S)-4-[(diMethylaMino)carbonyl]-2-[[(4,5,6,7-tetrahydro-5-Methylthiazolo[5,4-c]pyridin-2-yl)carbonyl]aMino]cyclohexyl]-;DU-176;Edoxaban(DU-176);Edoxaban N-(5-Chloro-2-pyridinyl)-N'-[(1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-[[(4,5,6,7-tetrahydro-5-methylthiazolo[5,4-c]pyridin-2-yl)carbonyl]amino]cyclohexyl]ethanediamide;5- chloro -2- pyridine -N, N-dimethyl formamidine
• CAS NO: 480449-70-5
• Molecular Formula: C24H30ClN7O4S
• Molecular Weight: 548.065
• EINECS: 1592732-453-0
• Mol File: 480449-70-5.mol
• Article Data: 31

Chemical Properties

• Appearance: /
• Density: 1.43
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly, Heated), Methanol (Slightly, Heated)
• PKA: 9.46±0.70(Predicted)
• CAS DataBase Reference: edoxaban(CAS DataBase Reference)
• NIST Chemistry Reference: edoxaban(480449-70-5)
• EPA Substance Registry System: edoxaban(480449-70-5)

Safety Data

• Hazardous Substances Data: 480449-70-5(Hazardous Substances Data)

Usage

Uses

oral factor Xa inhibitor

Definition

ChEBI: A monocarboxylic acid amide that is used (as its tosylate monohydrate) for the treatment of deep vein thrombosis and pulmonary embolism.

Indications

Edoxaban is a direct oral anticoagulant (DOAC). It exerts its effects by inhibiting factor Xa (FXa). Edoxaban was FDA approved in early 2015 to treat deep venous thrombosis, pulmonary embolism and decrease the risk of hypercoagulability related illness; stroke, and systemic embolism (SE) in subjects with nonvalvular atrial fibrillation (NVAF).When compared to the popularly used anticoagulant warfarin, edoxaban entails more limited monitoring and possesses a reduced risk for significant bleeding and fewer interactions with other agents.Edoxaban is the most current direct oral anticoagulant (DOAC) and does not associate with the CYP-450 system.Various clinical trials and studies (ENGAGE AF-TIMI and Hokusai-VTE) expressed edoxaban's effectiveness compared to the conventional vitamin K antagonist warfarin. It was demonstrated to be non-inferior in preventing blood clots when compared to warfarin. Edoxaban is the second FDA-approved anticoagulant agent with once-daily administration.Contrary to the other direct oral anticoagulants, apixaban and rivaroxaban, edoxaban has not yet received approval for secondary and postoperative prophylaxis for venous thromboembolism (VTE).FDA-Approved Indications:Deep venous thrombosisPulmonary embolismNonvalvular atrial fibrillation (NVAF)https://www.ncbi.nlm.nih.gov/

Pharmacology

Similar to rivaroxaban and apixaban,edoxaban is an orally active, small-molecule (548 Da), reversible factor Xa inhibitor.As with the other direct oral factor Xa inhibitors,edoxaban exhibits a 10,000-fold greater selectivity for factor Xa compared with other serine proteins such as factor VlIa, t-PA, plasmin,or trypsin.Administered as edoxaban tosylate,the compound competitively inhibits free factor Xa directly without the need for antithrombin and factor Xa incorporated in the prothrombinase complex. The concentration-dependent inhibition of factor Xa leads to reduced thrombin generation and thrombin-induced platelet aggregation. Edoxaban inhibited factor Xa with Ki values of 0.561 nM for free factor Xa and 2.98 nM for prothrombinase.128 Edoxaban exhibits linear pharmacokinetics and produces concentration-dependent increases in the PT,INR, and aPTT.However,changes in these laboratory assays with edoxaban tend to be unpredictable and highly variable, reducing their use as a monitoring tool in clinical practice.Pharmacokinetics and Pharmacodynamics of Edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting Factor XaLaboratory measurement of the anticoagulant activity of edoxaban: a systematic reviewPharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans

Drug interactions

The majority of edoxaban pharmacokinetic drug interactions result from inhibition or induction of the P-gp efflux transporter,which is responsible for intestinal transport.Edoxaban taken with quinidine demonstrates an increase in edoxaban Cmax of 85% and AUS of 77%.Coadministration with dronedarone resulted in a Cmax and AUC increase of 46% and 85%，respectively.This drug interaction also increased the 24-h edoxaban concentration by 158%.Additionally, verapamil increased the edoxaban Cmax by 53%, the AUC by 53%, and the 24-h edoxaban concentration by 29%.146 As per the phase 3 clinical trial, patients receiving quinidine, dronedarone,or verapamil should receive the reduced dose of 30 mg daily instead of 60 mg daily.It should be noted that patients receiving azole antifungal agents, such as ketoconazole, or protease inhibitors were excluded from the phase 3 trial because of concerns about increased edoxaban exposure.Conversely, the use of rifampin, a P-gp inducer, resulted in a significant 34% reduction in the edoxaban AUC.Therefore, the combination of rifampin and edoxaban should be avoided.

Upstream product

• 139893-81-5 (1S,4S,5S)-4-bromo-6-oxabicyclo<3.2.1>octan-7-one 
• 5708-19-0 (1S)-3-cyclohexenecarboxylic acid 
• 89580-42-7 3-bromo-1-methylpiperidin-4-one hydrobromide 
• 259809-24-0 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine 
• 720720-96-7 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine-2-carboxylic acid hydrochloric acid salt 
• 480452-37-7 N¹-[(1S,2R,4S)-2-amino-4-[(dimethylamino)carbonyl]cyclohexyl]-N²-(5-chloro-2-pyridyl)ethanediamide 
• 758685-72-2 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine-2-carboxylic acid 
• 1057650-82-4 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl chloride 
• 365998-36-3 (1S,2R,4S)-N₂-(tert-butoxycarbonyl)-4-(N,N-dimethylcarbamoyl)-1,2-cyclohexanediamine 

Downstream Products

• 480449-71-6 [14C]-Edoxaban tosylate 

Relevant articles and documents

PROCESS FOR PREPARATION OF EDOXABAN

The present invention relates to process for preparation N1-(5-Chloropyridin-2-yl)-N2-[(1S,2R,4S)-4-(N,N-dimethylcarbamoyl)-2-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-ylcarboxamido)cyclohexyl]oxamide p-toluene sulfonate monohydrate [edoxaban tosylate monohydrate], the compound of formula (I), comprising reacting compound of formula (VI) with compound of formula (V) to obtain the compound of formula (IV) and further converting it to edoxaban tosylate monohydrate in an industrially feasible process.

Methyltetrahydropyridinothiazole active compound and preparation method and application thereof

The invention relates to a methyltetrahydropyridinothiazole active compound (compound (I)) and a preparation method and application thereof. The preparation method comprises the following steps: making 5-methyl-4, 5, 6, 7-tetrahydro[1, 3]thiazolo[5, 4-c]p

Preparation method of high-purity edoxaban

The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of high-purity edoxaban. The existing process for synthesizing edoxaban generally has the problems of low product purity, high impurity content, single and low-efficiency purification means, more three wastes and the like, and urgently needs to solve the problems in industry to realize industrialization of the edoxaban. In order to solve the problem, the invention provides the method for industrially producing high-purity edoxaban. According to the method, a halogenated hydrocarbon and analcohol mixed solvent are used for recrystallizing the product, the quality of the product is improved, the impurity content is reduced, the liquid chromatographic purity of the product is not lower than 99.0%, the single impurity content does not exceed 0.1%, and the method provided by the invention is relatively high in yield, less in three wastes, good in product quality and suitable for industrial production.