Mitoxantrone

Bezeichnung:Mitoxantrone

CAS-Nr65271-80-9

Englisch Name:Mitoxantrone

CBNumberCB1246423

SummenformelC22H28N4O6

Molgewicht444.48

MOL-Datei65271-80-9.mol

Mitoxantrone physikalisch-chemischer Eigenschaften

Schmelzpunkt	170-1740C
Siedepunkt	554.47°C (rough estimate)
Dichte	1.3049 (rough estimate)
Brechungsindex	1.6500 (estimate)
storage temp.	Keep in dark place,Sealed in dry,2-8°C
Löslichkeit	DMSO (Slightly), Methanol (Sparingly), Water (Slightly)
pka	pKa 5.99 (Uncertain);8.13 (Uncertain)
Aggregatzustand	Solid
Farbe	Dark Blue to Black
CAS Datenbank	65271-80-9(CAS DataBase Reference)
IARC	2B (Vol. 76) 2000

Sicherheit

Kennzeichnung gefährlicher	T,T+
R-Sätze:	46-61-26/27/28
S-Sätze:	53-36/37/39-45-22
WGK Germany	3
RTECS-Nr.	CB5748500
HS Code	2922.50.2500

Gefahreninformationscode (GHS)

Mitoxantrone Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R46:Kann vererbbare Schäden verursachen.
R61:Kann das Kind im Mutterleib schädigen.
R26/27/28:Sehr giftig beim Einatmen, Verschlucken und Berührung mit der 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).
S22:Staub nicht einatmen.
Chemische Eigenschaften
Dark Blue Crystalline Solid
Originator
Novantrone,Immunex Corporation
Verwenden
A DNA intercalating drug. Inhibits DNA synthesis. Used as an anti-cancer agent
Verwenden
Mitoxantrone is a DNA intercalating drug. Mitoxantrone inhibits DNA synthesis. Mitoxantrone is used as an anti-cancer agent.
Definition
ChEBI: Mitoxantrone is a dihydroxyanthraquinone that is 1,4-dihydroxy-9,10-anthraquinone which is substituted by 6-hydroxy-1,4-diazahexyl groups at positions 5 and 8. It has a role as an antineoplastic agent and an analgesic.
Indications
Mitoxantrone (Novantrone) is a synthetic anthraquinone that is structurally and mechanistically related to the anthracyclines. It intercalates with DNA and produces single- strand DNA breakage. It is cross-resistant with doxorubicin in multidrug-resistant cells and in patients who have failed to respond to doxorubicin therapy.
Mitoxantrone is active against breast carcinomas, leukemias, and lymphomas. Its antitumor efficacy in patients with breast cancer is slightly lower than that of doxorubicin. Its major toxicity is myelosuppression; mucositis and diarrhea also may occur. Mitoxantrone produces less nausea, alopecia, and cardiac toxicity than does doxorubicin.
Manufacturing Process
A suspension of 12.5 g of 2-(2-aminoethylamino)ethanol in 40 ml of N,N,N',N'-tetramethylethylenediamine is stirred and de-aerated by bubbling nitrogen in for 15 min. A 10.97 g of leuco-1,4,5,8-tetrahydroxyanthraquinone is gradually added with stirring. The suspension is heated and stirred under nitrogen at 50-52°C for 5 hours. The mixture is allowed to stand and cool under nitrogen for 12 hours. The solid is collected by decantation, macerated in ethanol, collected and washed with ethanol giving 15.06 g of the desired product leuco-1,4-bis[2-(2-hydroxyethylamino)ethylamino]-5,8- dihydroxyanthraquinone as a green-gray solid, melting point 129-131°C.
Chloranil oxidation. To 17.86 g of a suspension of the leuco-1,4-bis[2-(2- hydroxyethylamino)ethylamino]-5,8-dihydroxyanthraquinone (0.03 mole) in 2- methoxyethanol was added gradually with stirring 15 ml of 8 N ethanolic hydrogen chloride. The system was chilled with an ice bath and stirred as 7.50 g (0.0305 mole) of chloranil powder was gradually added. The mixture was stirred overnight at room temperature and diluted with 600 ml of ether. The solid was collected and washed with tetrahydrofuran. Yield of 1,4-bis[2-(2- hydroxyethylamino)ethylamino]-5,8-dihydroxyanthraquinone dihydrochloride 21.34 g, melting point 203-205°C (without recrystallisation).
Trademarks
Novantrone (Serono).
Therapeutic Function
Antineoplastic
Mechanism of action
The mechanism of its action is not completely understood, although it is presumed, that mitoxantrone acts by binding with DNA, thus disturbing the twisting process of the chains. It is used intravenously for treating severe nonlymphatic leukemia, breast cancer, and so on. A synonym of this drug is novantrone.
Synthese
Mitoxantrone, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl) amino) ethyl]amino]]-9,10-anthracendione (30.6.3), is structurally related to the antibiotic doxorubicine. It is synthesized from danthron (1,8-dihydroxyanthraquinone), which when reacted with nitric acid, and then a mixture of sodium sulfide and thiosulfate in a base, is transformed to 1,4,5,8-tetrahydroxyanthraquinone (30.6.2). Reacting this with 2-aminoethylaminoethanol in the presence of chloranyl (2,3,5,6-tetrachlorobenzoquinone-1,4) gives the desired mitoxantrone (30.6.3),
Veterinary Drugs and Treatments
Mitoxantrone may be useful in the treatment of several neoplastic diseases in dogs and cats, including lymphosarcoma mammary adenocarcinoma, squamous cell carcinoma, renal adenocarcinoma, fibroid sarcoma, thyroid or transitional cell carcinomas, and hemangiopericytoma.
Because renal clearance of the drug is minimal (10%), it may be administered to cats with renal insufficiency much more safely than doxorubicin.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Other antineoplastic agents: enhanced myelosuppression - when used in combination reduce mitoxantrone dose by 2-4 mg/m2.
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.
Cardiotoxic drugs: increased risk of cardiac toxicity.
Ciclosporin: excretion of mitoxantrone reduced.
Live vaccines: risk of generalised infections - avoid.
Stoffwechsel
Extensive metabolism in the liver. Excretion is predominantly via the bile and faeces. 5-10% of a dose is excreted in the urine and 13-25% in the faeces, within 5 days

Mitoxantrone Upstream-Materialien And Downstream Produkte

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