Dronedarone

Base Information

• Chemical Name: Dronedarone
• CAS No.: 141626-36-0
• Molecular Formula: C31H44N2O5S
• Molecular Weight: 556.767
• Hs Code.: 3004909090
• European Community (EC) Number: 604-240-2
• UNII: JQZ1L091Y2
• DSSTox Substance ID: DTXSID3048653
• Nikkaji Number: J1.055.653H
• Wikipedia: Dronedarone
• Wikidata: Q408637
• NCI Thesaurus Code: C65485
• RXCUI: 233698
• Pharos Ligand ID: MFWXQ3S2LQB2
• Metabolomics Workbench ID: 57494
• ChEMBL ID: CHEMBL184412
• Mol file: 141626-36-0.mol

Synonyms:dronedarone;Multaq;SR 33589;SR 33589B

Chemical Property of Dronedarone

Chemical Property:

• Vapor Pressure: 1.47E-18mmHg at 25°C
• Melting Point: 65.3°
• Refractive Index: 1.563
• Boiling Point: 683.9 °C at 760 mmHg
• PKA: 7.40±0.30(Predicted)
• Flash Point: 367.4 °C
• PSA: 97.23000
• Density: 1.143 g/cm³
• LogP: 8.20280
• Storage Temp.: 2-8°C
• Solubility.: ≥27.84 mg/mL in DMSO; insoluble in H2O; ≥49.8 mg/mL in EtOH
• XLogP3: 7.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 18
• Exact Mass: 556.29709368
• Heavy Atom Count: 39
• Complexity: 800

Purity/Quality:

98%,99%, ^*data from raw suppliers

Dronedarone-d6HCl ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antiarrhythmic Agents
• Canonical SMILES: CCCCC1=C(C2=C(O1)C=CC(=C2)NS(=O)(=O)C)C(=O)C3=CC=C(C=C3)OCCCN(CCCC)CCCC
• Recent ClinicalTrials: Early Dronedarone Versus Usual Care to Improve Outcomes in Persons With Newly Diagnosed Atrial Fibrillation
• Recent EU Clinical Trials: First-line cryoablation for early treatment of Persistent Atrial Fibrillation – a randomized study comparing early trigger isolation using the Cryoballoon versus antiarrhythmic medication.
• Description: AF is the most common form of sustained cardiac arrhythmia, with an increasing prevalence in the aging population. AF accounts for 34.5% of arrhythmia-related hospital admissions in the United States. The most significant consequences of AF include congestive heart failure, a 5-fold increased risk of stroke, and increased rate of mortality. Although a 90% conversion rate from AF to normal sinus rhythm (NSR) can be achieved with electrical cardioversion, up to 70% of these patients require additional therapy with antiarrhythmic drugs in order to maintain NSR. Dronedarone, a close analog of amiodarone, is structurally modified to provide improved safety and pharmacokinetic profile. With the introduction of a sulfonamide group, dronedarone is less lipophilic, has lower tissue accumulation, and has a much shorter serum half-life (～24 h) compared with amiodarone. Additionally, dronedarone lacks the iodine moieties that are responsible for thyroid dysfunctions associated with amiodarone. Dronedarone is specifically indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent AF or AFL, with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents (including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine-activated potassium current, peak sodium current, and L-type calcium current) and exhibits antiadrenergic effects. Overall, dronedarone was well tolerated. The most common side effects were gastrointestinal in nature and included nausea, vomiting, and diarrhea.
• Clinical Use: Anti-arrhythmic:Maintenance of sinus rhythm after successful cardioversion in adult clinically stable patients with paroxysmal or persistent atrial fibrillation
• Drug interactions: Potentially hazardous interactions with other drugsAnti-arrhythmics: increased risk of myocardial depression with other anti-arrhythmics; increased risk of ventricular arrhythmias with amiodarone or disopyramide - avoid. Antibacterials: increased risk of ventricular arrhythmias with clarithromycin, telithromycin and erythromycin; concentration reduced by rifampicin - avoidAnticoagulants: increased anti-coagulant effect with coumarins and phenindione; increased dabigatran concentration - avoid; avoid with rivaroxaban; concentration of edoxaban increased - reduce dose of edoxaban.Antidepressants: concentration possibly reduced by St John’s wort - avoid; increased risk of ventricular arrhythmias with tricyclic antidepressants, citalopram and escitalopram - avoid.Antiepileptics: concentration possibly reduced by fosphenytoin, phenytoin, carbamazepine, phenobarbital and primidone - avoid.Antifungals: concentration increased by ketoconazole - avoid; avoid with itraconazole, posaconazole and voriconazole.Antipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval; increased risk of ventricular arrhythmias with phenothiazines - avoid.Antivirals: avoid with ritonavir; increased risk of ventricular arrhythmias with saquinavir - avoid.Beta-blockers: increased risk of myocardial depression; concentration of metoprolol and propranolol possibly increased; increased risk of ventricular arrhythmias with sotalol - avoid.Calcium channel blockers: concentration increased by nifedipine; increased risk of bradycardia and myocardial depression with diltiazem and verapamil.Cytotoxics: possibly increases bosutinib concentration - avoid or consider reducing bosutinib dose; possibly increases ibrutinib concentration - reduce ibrutinib doseDigoxin: increased concentration (halve digoxin maintenance dose).Fingolimod: possibly increased risk of bradycardia.Grapefruit juice: concentration of dronedarone increased - avoid.Lipid-lowering drugs: concentration of atorvastatin and rosuvastatin possibly increased; increased risk of myopathy with simvastatin; concentration of lomitapide possibly increased - avoid.Tacrolimus: manufacturer advises use with caution.

Technology Process of Dronedarone

There total 202 articles about Dronedarone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

N-(2-butyl-3-[4-(3-oxopropoxy)benzoyl]-1-benzofuran-5-yl)methanesulfonamide (1420180-98-8) + dibutylamine (111-92-2) → dronedarone (141626-36-0)

Guidance literature:

With hydrogen; In methanol; at 50 ℃; for 4h; under 7500.75 Torr; Reagent/catalyst; Solvent; Temperature; Time;

Reference yield: 100.0%

N-[2-butyl-3-(4-fluorobenzoyl)-1-benzofuran-5-yl]methanesulfonamide (1448297-06-0) + 3-dibutylamino-1-propanol sodium salt (1448297-07-1) → dronedarone (141626-36-0)

Guidance literature:

With copper(l) iodide; In N,N-dimethyl-formamide; at 90 - 100 ℃; for 25h;

Reference yield: 96.5%

3-dibutylaminopropanol (2050-51-3) + 4-({2-butyl-5-[(methylsulfonyl)amino]-1-benzofuran-3-yl}carbonyl)phenyl-4-[(methylsulfonyl)amino]benzenesulfonate (1448297-14-0) → dronedarone (141626-36-0)

Guidance literature:

With potassium hydroxide; In N,N-dimethyl-formamide; at 40 ℃; for 9h;

upstream raw materials:

dronedarone hydrochloride

(5-amino-2-butyl-benzofuran-3-yl)-[4-(3-dibutylamino-propoxy)-phenyl]-methanone

methanesulfonyl chloride

5-amino 3-[4-(3-di-n-butylamino-propoxy)benzoyl] 2-n-butyl benzofuran

Downstream raw materials:

dronedarone hydrochloride

dronedarone fumarate

2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl)-5-methansulfonylamino-benzofuran mesylate

Refernces

• 1、 Madhasu, Madhu,Doda, Sai Reddy,Begari, Prem Kumar,Dasari, Krishna Rao,Thalari, Gangadhar,Kadari, Sudhakar,Yadav, Jhillu Singh. "Concise total synthesis of antiarrhythmic drug dronedarone via a conjugate addition followed intramolecular heck cyclization". . p. 1861 - 1866. Retrieved 2021/07/09.
• 2、 Klucznik, Tomasz,Mikulak-Klucznik, Barbara,McCormack, Michael P.,Lima, Heather,Szymku?, Sara,Bhowmick, Manishabrata,Molga, Karol,Zhou, Yubai,Rickershauser, Lindsey,Gajewska, Ewa P.,Toutchkine, Alexei,Dittwald, Piotr,Startek, Micha? P.,Kirkovits, Gregory J.,Roszak, Rafa?,Adamski, Ariel,Sieredzińska, Bianka,Mrksich, Milan,Trice, Sarah L.J.,Grzybowski, Bartosz A.. "Efficient Syntheses of Diverse, Medicinally Relevant Targets Planned by Computer and Executed in the Laboratory". supporting information. p. 522 - 532. Retrieved 2018/03/21.