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AMIODARONE

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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 benzofuran 390 (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: FR 1339389; 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 names Cordarone, Nexterone
AHFS/Drugs.com monograph
MedlinePlus a687009
Pregnancy cat.
Legal status
  • Prescription only
Routes oral or intravenous
Pharmacokinetic data
Bioavailability 20–55%
Metabolism Liver
Half-life 58 days (range 15-142 days)
Excretion Primarily Hepatic and Biliary
Identifiers
CAS number 1951-25-3 Yes
ATC code C01BD01
PubChem CID 2157
IUPHAR ligand 2566
DrugBank DB01118
ChemSpider 2072 Yes
UNII N3RQ532IUT Yes
KEGG D02910 Yes
ChEBI CHEBI:2663 Yes
ChEMBL CHEMBL633 Yes
Chemical data
Formula C25H29I2NO3 
Mol. mass 645,31 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.

Amiodarone

    • ATC:C01BD01
  • Use:antiarrhythmic
  • Chemical name:(2-butyl-3-benzofuranyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone
  • Formula:C25H29I2NO3
  • MW:645.32 g/mol
  • CAS-RN:1951-25-3
  • EINECS:217-772-1
  • LD50:178 mg/kg (M, i.v.); >4 g/kg (M, p.o.)

Derivatives

hydrochloride

  • Formula:C25H29I2NO3 • HCl
  • MW:681.78 g/mol
  • CAS-RN:19774-82-4

Substance Classes

Synthesis Path

Substances Referenced in Synthesis Path

CAS-RN Formula Chemical Name CAS Index Name
100-07-2 C8H7ClO2 4-anisoyl chloride Benzoyl chloride, 4-methoxy-
271-89-6 C8H6O benzofuran Benzofuran
4265-27-4 C12H14O 2-butylbenzofuran Benzofuran, 2-butyl-
52490-15-0 C19H18O3 2-butyl-3-(4-hydroxybenzoyl)benzofuran Methanone, (2-butyl-3-benzofuranyl)(4-hydroxyphenyl)-
1951-26-4 C19H16I2O3 2-butyl-3-(4-hydroxy-3,5-diiodobenzoyl)benzofuran Methanone, (2-butyl-3-benzofuranyl)(4-hydroxy-3,5-diiodophenyl)-
83790-87-8 C20H20O3 2-butyl-3-(4-methoxybenzoyl)benzofuran Methanone, (2-butyl-3-benzofuranyl)(4-methoxyphenyl)-
106-31-0 C8H14O3 butyric anhydride Butanoic acid, anhydride
85614-50-2 C12H12O2 2-butyrylbenzofuran 1-Butanone, 1-(2-benzofuranyl)-
100-35-6 C6H14ClN 2-diethylaminoethyl chloride Ethanamine, 2-chloro-N,N-diethyl-

Trade Names

Country Trade Name Vendor Annotation
D Cordarex Sanofi-Aventis
Cornaron TAD Pharma
F Corbionax Ge Winthrop/Sanofi-Aventis
Cordarone Sanofi-Aventis
GB Cordaron Sanofi-Aventis
I Amiodar Sigma-Tau
Cordarone Sanofi-Aventis
J Ancaron Sanofi-Aventis
USA Cordarone Wyeth-Ayerst as hydrochloride

Formulations

  • inj. sol. 150 mg/3ml; tabl. 100 mg, 200 mg

References

    • FR 1 339 389 (Labaz; appl. 22.11.1962).
    • US 3 248 401 (Labaz; 26.4.1966; D-prior. 24.11.1961).
  • 2-butylbenzofuran:

    • Buu-Hoï, N.P. et al.: J. Chem. Soc. (JCSOA9) 1964, 173.
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1 Comment

  1. larryhbern says:

    I recall their using it in cardiothoracic surgery some 8 years ago at NY Methodist in Park Slope, Brooklyn, NY. I think that I had done the statistics for a presentation. I’ll have to check that.

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DR ANTHONY CRASTO

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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