141626-36-0 Usage
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.
Originator
Sanofi-Aventis (US)
Definition
ChEBI: A member of the class of 1-benzofurans used for the treatment of cardiac arrhythmias.
Brand name
Multaq
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.
Metabolism
Dronedarone is extensively metabolised in the liver,
mainly by the cytochrome P450 isoenzyme CYP3A4 to
a less active N-debutyl metabolite, and several inactive
metabolitesAbout 6% of an oral dose is excreted in the urine (entirely
metabolites) and 84% in the faeces (metabolites and
unchanged drug).
Check Digit Verification of cas no
The CAS Registry Mumber 141626-36-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,1,6,2 and 6 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 141626-36:
(8*1)+(7*4)+(6*1)+(5*6)+(4*2)+(3*6)+(2*3)+(1*6)=110
110 % 10 = 0
So 141626-36-0 is a valid CAS Registry Number.
InChI:InChI=1/C31H44N2O5S/c1-5-8-12-29-30(27-23-25(32-39(4,35)36)15-18-28(27)38-29)31(34)24-13-16-26(17-14-24)37-22-11-21-33(19-9-6-2)20-10-7-3/h13-18,23,32H,5-12,19-22H2,1-4H3
141626-36-0Relevant articles and documents
Convergent synthesis of dronedarone, an antiarrhythmic agent
Okitsu, Takashi,Ogasahara, Mizuki,Wada, Akimori
, p. 1149 - 1153 (2016)
We have developed a convergent synthesis of dronedarone, an antiarrhythmic agent. The key steps of the process are the construction of a benzofuran skeleton by iodocyclization and the carbonylative Suzuki-Miyaura cross-coupling for biaryl ketone formation. This synthetic route required only eight steps from 2-amino-4-nitrophenol in 23% overall yield.
Visible-Light-Induced Radical Carbo-Cyclization/ gem-Diborylation through Triplet Energy Transfer between a Gold Catalyst and Aryl Iodides
Hashmi, A. Stephen K.,Rominger, Frank,Si, Xiaojia,Zhang, Lumin
, p. 10485 - 10493 (2020/07/03)
Geminal diboronates have attracted significant attention because of their unique structures and reactivity. However, benzofuran-, indole-, and benzothiophene-based benzylic gem-diboronates, building blocks for biologically relevant compounds, are unknown. A promising protocol using visible light and aryl iodides for constructing valuable building blocks, including benzofuran-, indole-, and benzothiophene-based benzylic gem-diboronates, via radical carbo-cyclization/gem-diborylation of alkynes with a high functional group tolerance is presented. The utility of these gem-diboronates has been demonstrated by a 10 g scale conversion, by versatile transformations, by including the synthesis of approved drug scaffolds and two approved drugs, and even by polymer synthesis. The mechanistic investigation indicates that the merging of the dinuclear gold catalyst (photoexcitation by 315-400 nm UVA light) with Na2CO3 is directly responsible for photosensitization of aryl iodides (photoexcitation by 254 nm UV light) with blue LED light (410-490 nm, λmax = 465 nm) through an energy transfer (EnT) process, followed by homolytic cleavage of the C-I bond in the aryl iodide substrates.
A short synthesis of Dronedarone
Piotrkowska, Barbara,Nerdinger, Sven,Schreiner, Erwin,Seli?, Lovro,Graczyk, Piotr P.
, p. 4330 - 4335 (2018/05/04)
A modification of the Nenitzescu reaction was used to obtain Dronedarone from quinonimine 20 and 1,3-diketone 14 (R = CH2CH2CH2NBu2) in a two-stage process in almost 55% overall yield. Our results represent significant improvement over other state-of-the-art methods as no extra steps for the decoration of the benzofuran core are required.
