Triethylenetetramine

Last updated
Triethylenetetramine
N1,N1'-(ethane-1,2-diyl)bis(ethane-1,2-diamine) 200.svg
Triethylenetetramine-3D-balls.png
Triethylenetetramine-3D-spacefill.png
Names
Preferred IUPAC name
N1,N1′-(Ethane-1,2-diyl)di(ethane-1,2-diamine)
Other names
  • N,N'-Bis(2-aminoethyl)ethane-1,2-diamine
  • TETA
  • trien
  • trientine (INN)
  • trientine dihydrochloride
  • MK-0681
Identifiers
3D model (JSmol)
605448
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.003.591 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 203-950-6
27008
KEGG
MeSH Trientine
PubChem CID
RTECS number
  • YE6650000
UNII
UN number 2259
  • InChI=1S/C6H18N4/c7-1-3-9-5-6-10-4-2-8/h9-10H,1-8H2 Yes check.svgY
    Key: VILCJCGEZXAXTO-UHFFFAOYSA-N Yes check.svgY
  • NCCNCCNCCN
Properties
C6H18N4
Molar mass 146.238 g·mol−1
AppearanceColorless liquid
Odor Fishy, ammoniacal
Density 982 mg mL−1
Melting point −34.6 °C; −30.4 °F; 238.5 K
Boiling point 266.6 °C; 511.8 °F; 539.7 K
Miscible
log P 1.985
Vapor pressure <1 Pa (at 20 °C)
1.496
Thermochemistry
376 J K−1 mol−1 (at 60 °C)
Hazards
GHS labelling:
GHS-pictogram-acid.svg GHS-pictogram-exclam.svg
Danger
H312, H314, H317, H412
P273, P280, P305+P351+P338, P310
Flash point 129 °C (264 °F; 402 K)
Lethal dose or concentration (LD, LC):
  • 550 mg kg−1(dermal, rabbit)
  • 2.5 g kg−1(oral, rat)
Pharmacology
Legal status
Related compounds
Related amines
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Triethylenetetramine (TETA and trien), also known as trientine (INN) when used medically, is an organic compound with the formula [CH2NHCH2CH2NH2]2. The pure freebase is a colorless oily liquid, but, like many amines, older samples assume a yellowish color due to impurities resulting from air-oxidation. It is soluble in polar solvents. The branched isomer tris(2-aminoethyl)amine and piperazine derivatives may also be present in commercial samples of TETA. [3] The hydrochloride salts are used medically as a treatment for copper toxicity.

Contents

Uses

Epoxy uses

The reactivity and uses of TETA are similar to those for the related polyamines ethylenediamine and diethylenetriamine. It is primarily used as a crosslinker ("hardener") in epoxy curing. [4] [5] TETA, like other aliphatic amines, react quicker and at lower temperatures than aromatic amines due to less negative steric effects since the linear nature of the molecule provides it the ability to rotate and twist.

Medical uses

Trientine
Clinical data
Trade names Syprine, Cuprior, Cufence, others
AHFS/Drugs.com Monograph
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
  • (2-aminoethyl)({2-[(2-aminoethyl)amino]ethyl})amine
DrugBank
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.003.591 OOjs UI icon edit-ltr-progressive.svg

The hydrochloride salt of TETA, referred to as trientine hydrochloride, is a chelating agent that is used to bind and remove copper in the body to treat Wilson's disease, particularly in those who are intolerant to penicillamine. [11] Some recommend trientine as first-line treatment, but experience with penicillamine is more extensive. [16]

Trientine hydrochloride (brand name Syprine) was approved for medical use in the United States in November 1985. [11]

Trientine tetrahydrochloride (brand name Cuprior) was approved for medical use in the European Union in September 2017. [14] It is indicated for the treatment of Wilson's disease in adults, adolescents and children five years of age or older who are intolerant to D-penicillamine therapy. [14]

Trientine dihydrochloride (brand name Cufence) was approved for medical use in the European Union in July 2019. [15] It is indicated for the treatment of Wilson's disease in adults, adolescents and children five years of age or older who are intolerant to D-penicillamine therapy. [15]

The most common side effects include nausea, especially when starting treatment, skin rash, duodenitis (inflammation of the duodenum, the part of the gut leading out of the stomach), and severe colitis (inflammation in the large bowel causing pain and diarrhea). [15]

Society and culture

Controversies

In the United States, Valeant Pharmaceuticals International raised the price of its Syprine brand of TETA from $625 to $21,267 for 100 pills over five years. [17] The New York Times said that this "egregious" price increase caused public outrage. [17] Teva Pharmaceuticals developed a generic, which patients and doctors expected to be cheaper, but when it was introduced in February 2018, Teva's price was $18,375 for 100 pills. [17] Aaron Kesselheim, who studies drug pricing at Harvard Medical School, said that drug companies price the product at what they think the market will bear. [17]

Production

TETA is prepared by heating ethylenediamine or ethanolamine/ammonia mixtures over an oxide catalyst. This process gives a variety of amines, especially ethylene amines which are separated by distillation and sublimation. [4] [18]

Coordination chemistry

TETA is a tetradentate ligand in coordination chemistry, where it is referred to as trien. [19] Octahedral complexes of the type M(trien)L2 can adopt several diastereomeric structures. [20]

Related Research Articles

<span class="mw-page-title-main">Diltiazem</span> Calcium channel blocker medication

Diltiazem, sold under the brand name Cardizem among others, is a nondihydropyridine calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be used. It is taken by mouth or injection into a vein. When given by injection, effects typically begin within a few minutes and last a few hours.

<span class="mw-page-title-main">Penicillamine</span> Chemical compound

Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with kidney stones who have high urine cystine levels, rheumatoid arthritis, and various heavy metal poisonings. It is taken by mouth.

<span class="mw-page-title-main">Alemtuzumab</span> Medication

Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia and multiple sclerosis. In chronic lymphocytic leukemia, it has been used as both a first line and second line treatment. It is given by injection into a vein.

<span class="mw-page-title-main">Ethylenediamine</span> Chemical compound

Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately 500,000 tonnes produced in 1998. Ethylenediamine is the first member of the so-called polyethylene amines.

<span class="mw-page-title-main">Cysteamine</span> Chemical compound

Cysteamine is an organosulfur compound with the formula HSCH2CH2NH2. A white, water-soluble solid, it contains both an amine and a thiol functional groups. It is often used as salts of the ammonium derivative [HSCH2CH2NH3]+ including the hydrochloride, phosphocysteamine, and the bitartrate.The intermediate pantetheine is broken down into cysteamine and pantothenic acid.

A diamine is an amine with exactly two amino groups. Diamines are used as monomers to prepare polyamides, polyimides, and polyureas. The term diamine refers mostly to primary diamines, as those are the most reactive.

<span class="mw-page-title-main">Rasagiline</span> Chemical compound

Rasagiline is an irreversible inhibitor of monoamine oxidase-B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases.

<span class="mw-page-title-main">Palonosetron</span> Pharmaceutical drug

Palonosetron, sold under the brand name Aloxi, is a medication used for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is a 5-HT3 antagonist.

Pazopanib, sold under the brand name Votrient, is an anti-cancer medication marketed worldwide by Novartis. It is a potent and selective multi-targeted receptor tyrosine kinase inhibitor that blocks tumour growth and inhibits angiogenesis. It has been approved for renal cell carcinoma and soft tissue sarcoma by numerous regulatory administrations worldwide.

<span class="mw-page-title-main">Rilpivirine</span> HIV treatment

Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs such as efavirenz.

<span class="mw-page-title-main">Tris(2-aminoethyl)amine</span> Chemical compound

Tris(2-aminoethyl)amine is the organic compound with the formula N(CH2CH2NH2)3. This colourless liquid is soluble in water and is highly basic, consisting of a tertiary amine center and three pendant primary amine groups. Tris(2-aminoethyl)amine is commonly abbreviated as tren or TREN. It is used a crosslinking agent in the synthesis of polyimine networks and a tripodal ligand in coordination chemistry.

<span class="mw-page-title-main">Isavuconazonium</span> Chemical compound

Isavuconazonium sulfate, sold under the brand name Cresemba, is a systemic antifungal medication of the triazole class which is used to treat invasive aspergillosis and mucormycosis.

<span class="mw-page-title-main">Tofacitinib</span> Medication

Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer.

<span class="mw-page-title-main">Fedratinib</span> Chemical compound

Fedratinib, sold under the brand name Inrebic, is an anti-cancer medication used to treat myeloproliferative diseases including myelofibrosis. It is used in the form of fedratinib hydrochloride capsules that are taken by mouth. It is a semi-selective inhibitor of Janus kinase 2 (JAK-2). It was approved by the FDA on 16 August 2019.

Insulin degludec/liraglutide, sold under the brand name Xultophy, is a fixed-dose combination medication for the treatment of adults with type 2 diabetes to improve glycemic control in combination with diet and exercise. It contains insulin degludec and liraglutide. It is administered by subcutaneous injection.

<span class="mw-page-title-main">Etirinotecan pegol</span> Pharmaceutical drug

Etirinotecan pegol is a drug developed by Nektar Therapeutics for the treatment of certain kinds of breast cancer with brain metastases. The European Medicines Agency refused to grant it a marketing authorisation in 2017.

<span class="mw-page-title-main">Capmatinib</span> Chemical compound

Capmatinib, sold under the brand name Tabrecta, is an anticancer medication used for the treatment of metastatic non-small cell lung cancer whose tumors have a mutation that leads to the exon 14 skipping of the MET gene, which codes for the membrane receptor HGFR.

Burosumab, sold under the brand name Crysvita, is a human monoclonal antibody medication approved 2018 for the treatment of X-linked hypophosphatemia and tumor-induced osteomalacia.

<span class="mw-page-title-main">Deutetrabenazine</span> Chemical compound

Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor which is used for the treatment of chorea associated with Huntington's disease and tardive dyskinesia.

<span class="mw-page-title-main">Fosnetupitant</span> Chemical compound

Fosnetupitant is a medication used for the treatment of chemotherapy-induced nausea and vomiting. It is a prodrug of netupitant. It is used in combination with palonosetron hydrochloride and formulated as the salt fosnetupitant chloride hydrochloride for intravenous use.

References

  1. ↑ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada . 3 August 2022. Retrieved 25 March 2024.
  2. ↑ "Regulatory Decision Summary for Waymade-Trientine". Health Canada . 20 April 2021. Retrieved 25 March 2024.
  3. ↑ "Ethyleneamines" (PDF). Huntsman. 2007. Archived from the original (PDF) on 2019-03-06. Retrieved 2016-07-10.
  4. 1 2 Eller K, Henkes E, Rossbacher R, Höke H (2005). "Amines, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a02_001. ISBN   3527306730.
  5. ↑ "Triethylenetetramine". webbook.nist.gov. Retrieved 2022-07-20.
  6. 1 2 "Trientine Waymade". Therapeutic Goods Administration (TGA). 25 January 2021. Retrieved 8 September 2021.
  7. 1 2 "AusPAR: Trientine dihydrochloride". Therapeutic Goods Administration (TGA). 3 May 2021. Retrieved 8 September 2021.
  8. ↑ "Summary Basis of Decision (SBD) for Mar-Trientine". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  9. ↑ "Cuprior 150 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). Retrieved 21 September 2020.
  10. ↑ "Trientine dihydrochloride Tillomed 250 mg capsules, hard - Summary of Product Characteristics (SmPC)". (emc). Retrieved 21 September 2020.
  11. 1 2 3 "Syprine- trientine hydrochloride capsule". DailyMed. 22 December 2016. Retrieved 21 September 2020.
  12. ↑ "Trientine hydrochloride capsule". DailyMed. 28 February 2020. Retrieved 21 September 2020.
  13. ↑ "Cuvrior- trientine tetrahydrochloride tablet, film coated". DailyMed. 20 May 2022. Retrieved 21 January 2023.
  14. 1 2 3 "Cuprior EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 21 September 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  15. 1 2 3 4 "Cufence EPAR". European Medicines Agency (EMA). 24 May 2019. Retrieved 21 September 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  16. ↑ Roberts EA, Schilsky ML (June 2003). "A practice guideline on Wilson disease" (pdf). Hepatology. 37 (6): 1475–92. doi: 10.1053/jhep.2003.50252 . PMID   12774027. S2CID   263620.[ dead link ]
  17. 1 2 3 4 Thomas K (23 February 2018). "Patients Eagerly Awaited a Generic Drug. Then They Saw the Price". The New York Times . Retrieved 21 September 2020.
  18. ↑ Brydson JA (1999). "Epoxide Resins". In Brydson JA (ed.). Plastics Materials (Seventh ed.). Oxford: Butterworth-Heinemann. pp.  744–777. doi:10.1016/B978-075064132-6/50067-X. ISBN   9780750641326.
  19. ↑ von Zelewsky A (1995). Stereochemistry of Coordination Compounds . Chichester: John Wiley. ISBN   047195599X.
  20. ↑ Utsuno S, Sakai Y, Yoshikawa Y, Yamatera H (1985). "Three Isomers of the Trans -Diammine-[N,N′-bis(2-Aminoethyl)-1,2-Ethanediamine]-Cobalt(III) Complex Cation". Three Isomers of the trans-Diammine-[N,N′-bis(2-Aminoethyl)-1,2-Ethanediamine]-Cobalt(III) Complex Cation. Inorganic Syntheses. Vol. 23. pp. 79–82. doi:10.1002/9780470132548.ch16. ISBN   9780470132548.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.