Tuesday, 16 September 2014

Amiodarone


Amiodarone
Amiodarone structure.svg
Amiodarone
CAS : 1951-25-3
 (2-Butyl-3-benzofuranyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone
2-butyl-3-benzofuranyl-4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl ketone; 2-butyl-3-[3,5-diiodo-4-(b-diethylaminoethoxy)benzoyl]benzofuran
Molecular Formula: C25H29I2NO3
Molecular Weight: 645.31
Percent Composition: C 46.53%, H 4.53%, I 39.33%, N 2.17%, O 7.44%
In December 1985, amiodarone was approved by the FDA for the treatment of arrhythmias.[6] This makes amiodarone one of the few drugs approved by the FDA without rigorous randomized clinical trials.
Amiodarone is an antiarrhythmic agent used for various types of cardiac dysrhythmias, both ventricular and atrial. It was discovered in 1961. Despite relatively common side-effects, it is used in arrhythmias that are otherwise difficult to treat with medication.



A more recent synthesis of amiodarone reports the cyclisation of α-phenoxyhexanal 389 under acidic conditions to yield the substituted benzofuran390 (Scheme 76). A Friedel–Crafts acylation next introduces the aryl ring at the 3-position. Demethylation, iodination and a final alkylation with a diethylaminoethane fragment yields amiodarone [115-117].
  1. 115   Witczak, M.; Kwiecień, H. Synth. Commun. 2005, 35, 2223–2230.doi:10.1080/00397910500182747
    Return to citation in text: [1]
  2. Wang, Z. J. Synthetic Process for 2-Butyl-3-(hydroxy-3,5-diiodobenzoyl)-benzofuran. Chin. Patent 1,858,042, Nov 8, 2006……….116
    Return to citation in text: [1]
  3. Ha, H. R.; Stieger, B.; Grassi, G.; Altorfer, H. R.; Follath, F.Eur. J. Clin. Pharmacol. 2000, 55, 807–814.doi:10.1007/s002280050701….117
[1860-5397-7-57-i76]
Scheme 76: Synthesis of amiodarone……….http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-7-57#S76
Literature References:
Benzofuran derivative with multiple electrophysiological effects. Prepn: FR1339389; R. Tondeur, F. Binon,US 3248401 (1963, 1966 to Soc. Belge l’Azote Prod. Chim. Marly).
Physicochemical properties: M. Bonati et al., J. Pharm. Sci. 73,829 (1984).
HPLC determn in plasma: M. De Smet, D. L. Massart, J. Pharm. Biomed. Anal.6, 277 (1988).
Comprehensive description: T. A. Plomp, Anal. Profiles Drug Subs. 20, 1-120 (1991).
Review of pharmacology, clinical efficacy and safety: M. Chow, Ann. Pharmacother. 30, 637-643 (1996); B. N. Singh, Clin. Cardiol. 20, 608-618 (1997).
Clinical trial in cardiac resuscitation: P. J. Kudenchuk et al., N. Engl. J. Med.341, 871 (1999); to prevent atrial fibrillation: D. Roy et al., ibid. 342, 913 (2000).

External links

Amiodarone 3d balls.png
SYSTEMATIC (IUPAC) NAME
(2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-2,6-diiodophenoxy}ethyl)diethylamine
CLINICAL DATA
TRADE NAMESCordarone, Nexterone
AHFS/DRUGS.COMmonograph
MEDLINEPLUSa687009
PREGNANCY CAT.
LEGAL STATUS
  • ℞ Prescription only
ROUTESoral or intravenous
PHARMACOKINETIC DATA
BIOAVAILABILITY20–55%
METABOLISMLiver
HALF-LIFE58 days (range 15-142 days)
EXCRETIONPrimarily Hepatic and Biliary
IDENTIFIERS
CAS NUMBER1951-25-3 Yes
ATC CODEC01BD01
PUBCHEMCID 2157
IUPHAR LIGAND2566
DRUGBANKDB01118
CHEMSPIDER2072 Yes
UNIIN3RQ532IUT Yes
KEGGD02910 Yes
CHEBICHEBI:2663 Yes
CHEMBLCHEMBL633 Yes
CHEMICAL DATA
FORMULAC25H29I2NO3 
MOL. MASS645,31 g/mol
Derivative Type: Hydrochloride
CAS Registry Number: 19774-82-4
Manufacturers’ Codes: L-3428
Trademarks: Amiodar (Sanofi Winthrop); Ancaron (Taisho); Cordarex (Sanofi Winthrop); Cordarone (Wyeth); Ortacrone (Sanofi Winthrop); Pacerone (Upsher-Smith); Tachydaron (AWD); Trangorex (Sanofi Winthrop)
Molecular Formula: C25H29I2NO3.HCl
Molecular Weight: 681.77
Percent Composition: C 44.04%, H 4.44%, I 37.23%, N 2.05%, O 7.04%, Cl 5.20%
Properties: Crystalline powder, mp 156°. Also reported as crystals from acetone, mp 159 ±2° (Bonati). Soly at 25° (g/100ml): chloroform 44.51; methylene chloride 19.20; methanol 9.98; ethanol 1.28; benzene 0.65; tetrahydrofuran 0.60; acetonitrile 0.32; 1-octanol 0.30; ether 0.17; 1-propanol 0.13; water 0.07; hexane 0.03 petroleum ether 0.001. Sparingly sol in isopropanol; slightly sol in acetone, dioxane, and carbon tetrachloride. pH (5% soln) 3.4-3.9. pKa (25°C) 6.56 ±0.06. uv max (methanol): 208, 242 nm (E1%1cm 662 ±8, 623 ±10).
Melting point: mp 156°; mp 159 ±2° (Bonati)
pKa: pKa (25°C) 6.56 ±0.06
Absorption maximum: uv max (methanol): 208, 242 nm (E1%1cm 662 ±8, 623 ±10)
Therap-Cat: Antiarrhythmic (class III).
Keywords: Antiarrhythmic.
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