(Z)-(2-(4-(1,2-Diphenylbut-1-enyl)phenoxy)dimethylammonium-dihydrogen-2-hydroxypropan-1,2,3-tricarboxylat

Bezeichnung:(Z)-(2-(4-(1,2-Diphenylbut-1-enyl)phenoxy)dimethylammonium-dihydrogen-2-hydroxypropan-1,2,3-tricarboxylat

CAS-Nr54965-24-1

Englisch Name:Tamoxifen citrate

CBNumberCB7853805

SummenformelC32H37NO8

Molgewicht563.64

MOL-Datei54965-24-1.mol

Synonyma

(Z)-(2-(4-(1,2-Diphenylbut-1-enyl)phenoxy)dimethylammonium-dihydrogen-2-hydroxypropan-1,2,3-tricarboxylat

(Z)-(2-(4-(1,2-Diphenylbut-1-enyl)phenoxy)dimethylammonium-dihydrogen-2-hydroxypropan-1,2,3-tricarboxylat physikalisch-chemischer Eigenschaften

Schmelzpunkt	140-144 °C
storage temp.	2-8°C
Löslichkeit	methanol: soluble50mg/mL, clear, colorless
Aggregatzustand	Powder
Farbe	White to off-white
Wasserlöslichkeit	slightly soluble
Sensitive	Light Sensitive & Hygroscopic
Merck	14,9048
BCS Class	1
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
InChIKey	FQZYTYWMLGAPFJ-OQKDUQJOSA-N
SMILES	C(/C1=CC=CC=C1)(\C1C=CC(OCCN(C)C)=CC=1)=C(/CC)\C1=CC=CC=C1.C(O)(C(=O)O)(CC(=O)O)CC(=O)O
CAS Datenbank	54965-24-1(CAS DataBase Reference)
EPA chemische Informationen	Tamoxifen citrate (54965-24-1)

Sicherheit

Kennzeichnung gefährlicher	T,Xi
R-Sätze:	45-60-61-22-64-36/37/38
S-Sätze:	53-36/37/39-45-36-26
RIDADR	UN 3077 9 / PGIII
WGK Germany	3
RTECS-Nr.	KH2387000
HazardClass	IRRITANT
HS Code	29225090
Toxizität	LD50 in mice, rats (mg/kg): 200, 600 i.p.; 62.5, 62.5 i.v.; 3000-6000, 1200-2500 orally (Furr, Jordan)

Gefahreninformationscode (GHS)

Tamoxifen citrate Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R45:Kann Krebs erzeugen.
R60:Kann die Fortpflanzungsfähigkeit beeinträchtigen.
R61:Kann das Kind im Mutterleib schädigen.
R22:Gesundheitsschädlich beim Verschlucken.
R64:Kann Säuglinge über die Muttermilch schädigen.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
Beschreibung
Tamoxifen is a non-steroidal compound with structural similarities to diethylstilbestrol. Tamoxifen citrate is an estrogen receptor antagonist/partial agonist. Induces oxidative stress and apoptosis in estrogen receptor-negative cancer cell lines. Displays neuroprotective effects in permanent focal ischemia. Inhibits PKC. Potent agonist at GPR30 (membrane estrogen receptor). Clinically useful breast cancer agent.
Chemische Eigenschaften
Tamoxifen citrate is a white to off-white powder with no smell. It can dissolve in methanol, ethanol, and acetone to varying degrees and can slightly dissolve in trichloromethane, but it is almost insoluble in water. It can dissolve in glacial acetic acid. When tamoxifen citrate reaches a temperature between 142-148°C, it melts and decomposes at the same time.
Originator
Nolvadex,I.C.I.,UK,1973
Verwenden
anti-estrogen, protein kinase C inhibitor, beneficial cardiovascular effects, bone cancer treatment, induces DNA adduct formation
Verwenden
Tamoxifen citrate is commonly used in the treatment of women with metastatic carcinoma of the breast to prevent recurrence after surgery or radiation treatment, and as prophylaxis for patients at very high risk to develop breast cancer.
Verwenden
Tamoxifen Citrate is a selective estrogen response modifier (SERM), protein kinase C inhibitor and anti-angiogenetic factor. Tamoxifen is a prodrug that is metabolized to active metabolites 4-hydroxytamoxifen (4-OHT) and endoxifen by cytochrome P450 isoforms CYP2D6 and CYP3A4.
Manufacturing Process
To the Grignard reagent prepared from 0.59 part of magnesium, 3.95 parts of bromobenzene and 50 parts of ether there are added 7.5 parts of 4-(β- dimethylaminoethoxy)-α-ethyldesoxybenzoin in 50 parts of ether. After heating under reflux for 3 hours, the mixture is decomposed by the addition of a solution of 60 parts of ammonium chloride in 150 parts of water. The mixture is separated, and the ethereal layer is dried with anhydrous sodium sulfate, and the ether is evaporated. The residue is crystallized from methanol. There is thus obtained 1-(p-β-dimethylaminoethoxyphenyl)-1,2- diphenylbutan-1-ol, melting point 120°C to 121°C.
2.15 parts of 1-(p-β-dimethylaminoethoxyphenyl)-1,2-diphenylbutan-1-ol, 25 parts of ethanol and 0.8 part of 10 N hydrochloric acid are heated together under reflux for 3 hours. The solution is evaporated to dryness under reduced pressure and the residue is extracted with methylene chloride. The methylene chloride extract is decolorized with charcoal and then evaporated to dryness. The residue is dissolved in 100 parts of water, the solution is basified by the addition of sodium hydroxide solution, and the precipitated solid is extracted three times, each time with 50 parts of ether. The combined extracts are dried with anhydrous sodium sulfate and then evaporated. The residue is crystallized from aqueous methanol, and there is thus obtained 1-(p-β- dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene, melting point 95°C to 96°C.
Trademarks
Nolvadex (AstraZeneca); Soltamox (Savient).
Therapeutic Function
Antiestrogen, Antineoplastic
Allgemeine Beschreibung
Tamoxifen, 2-[4-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine(Nolvadex), is a triphenylethylene SERM used to treatearly and advanced breast carcinoma in postmenopausalwomen. Tamoxifen is used as adjuvant treatment for breastcancer in women following mastectomy and breast irradiation.It reduces the occurrence of contralateral breast cancerin patients receiving adjuvant tamoxifen therapy. It is alsoeffective in the treatment of metastatic breast cancer in bothwomen and men. In premenopausal women with metastaticbreast cancer, tamoxifen is an alternative to oophorectomyor ovarian irradiation. Tamoxifen can be used preventativelyto reduce the incidence of breast cancer in women athigh risk. Antiestrogenic and estrogenic side effects caninclude hot flashes, nausea, vomiting, platelet reduction,and (in patients with bone metastases) hypercalcemia. Likeall triphenylethylene derivatives, it should be protectedfrom light.
Biologische Aktivität
Estrogen receptor antagonist/partial agonist. Selective and potent inhibitor of mammalian sterol isomerase. Neuroprotective in female rats in vivo . Also high affinity agonist at the membrane estrogen receptor GPR30.
Biochem/physiol Actions
Cell permeable: yes
Sicherheitsprofil
Confirmed human carcinogen with experimental carcinogenic data. Poison by intraperitoneal route. Moderately toxic by ingestion. Experimental reproductive effects. Human systemic effects: visual field changes, retinal changes. An anti-estrogenic drug. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx.
Stoffwechsel
The major metabolite of tamoxifen is N-desmethyltamoxifen,which reaches steady-state levels higher than tamoxifenitself. It is believed that N-desmethyltamoxifen contributessignificantly to the overall antiestrogenic effect. Anothermetabolite, 4-hydroxytamoxifen, is a more potent antiestrogenthan tamoxifen, but because it is only a minor metaboliteof tamoxifen, it probably does not contribute significantly tothe therapeutic effects. 4-Hydroxytamoxifen, with its greateraffinity for the ERs, however, has been used extensively inpharmacological studies of these receptors. Tamoxifen concentrationsare reduced if coadministered with rifampin, a cytochromeP450 inducer.
Lager
+4°C
Einzelnachweise
1) Ferlini et al. (1999), Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell lines; Br. J. Cancer, 79 257
2) Kimelberg et al. (2003), Neuroprotective activity of tamoxifen in permanent focal ischemia; J. Neurosurg., 99 138
3) Couldwell et al. (1994), Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines; FEBS Lett., 345 43
4) Thomas et al. (2005), Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells; Endocrinology, 146 624
5) Jordan et al. (2006), Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer; Br. J. Pharmacol., 147 S269

Tamoxifen citrate Upstream-Materialien And Downstream Produkte

(Z)-(2-(4-(1,2-Diphenylbut-1-enyl)phenoxy)dimethylammonium-dihydrogen-2-hydroxypropan-1,2,3-tricarboxylat Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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