70476-82-3

Basic information

• Product Name: Mitoxantrone hydrochloride
• Synonyms: 1,4-dihydroxy-5,8-bis(2-(2-hydroxyethylamino)ethylamino)anthracene-9,10-dione dihydrochloride;Mitoxantrone hydrochloride 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthraquinone dihydrochloride;Mitoxantrone dihydrochloride, >=99%;DHAQ;DHAQ DIHYDROCHLORIDE;1,4-DIHYDROXY-5,8-BIS[2-[(2-HYDROXYETHYL)AMINO]ETHYL]AMINO]-9,10-ANTHRACENEDIONE DIHYDROCHLORIDE;1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthraquinone dihydrochloride;novantrone
• CAS NO: 70476-82-3
• Molecular Formula: C₂₂H₂₈N₄O₆*2ClH
• Molecular Weight: 517.4028
• EINECS: 274-619-1
• Product Categories: API;NOVALDIN;Anti-cancer&immunity;API's
• Mol File: 70476-82-3.mol
• Article Data: 5

Chemical Properties

• Melting Point: 203-205 C
• Boiling Point: 805.7 °C at 760 mmHg
• Flash Point: 441.1 °C
• Appearance: /
• Storage Temp.: 2-8°C
• Solubility: Sparingly soluble in water, slightly soluble in methanol, practically insoluble in acetone.
• Water Solubility: Soluble to 5 mM in water and to 75 mM in DMSO
• CAS DataBase Reference: Mitoxantrone hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Mitoxantrone hydrochloride(70476-82-3)
• EPA Substance Registry System: Mitoxantrone hydrochloride(70476-82-3)

Safety Data

• Hazard Codes: T,T+
• Statements: 46-61-26/27/28
• Safety Statements: 53-36/37/39-45-22
• RIDADR: 3249
• WGK Germany: 3
• RTECS: CB5748500
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 70476-82-3(Hazardous Substances Data)

Usage

Description

Mitoxantrone hydrochloride, also known as Novantrone, is a synthetic anthracenedione derivative related to doxorubicin. It is a dark blue, electrostatic, and hygroscopic powder that intercalates in DNA and inhibits topoisomerase II, thus inhibiting cell proliferation. Mitoxantrone hydrochloride is also an inhibitor of HIV-1 integrase and is less cardiotoxic than doxorubicin. It is supplied as a blue aqueous solution for intravenous administration and is used in the treatment of various types of cancer and multiple sclerosis.

Uses

Used in Oncology:
Mitoxantrone hydrochloride is used as an antineoplastic agent for the treatment of acute nonlymphocytic leukemia, including myelogenous promyelocytic, monocytic, and erythroid acute leukemias. It is also used in the treatment of advanced localized and metastatic mammary carcinomas, prostate cancer, non-Hodgkin's lymphoma, and multiple sclerosis.
Used in Antiviral Applications:
Mitoxantrone hydrochloride is used as an antiviral agent, specifically against HIV-1, by inhibiting the integrase enzyme (IC50 = 3.8 μM).
Used in Drug Delivery Systems:
Formulations containing mitoxantrone hydrochloride have been employed to improve the delivery, bioavailability, and therapeutic outcomes of the drug in the treatment of cancer and multiple sclerosis. Mitoxantrone is exported from cells in an ATPand glutathione-dependent manner by multidrug resistance protein-1, which may have implications for drug delivery and resistance mechanisms.

Originator

Lederle (USA)

Therapeutic Function

Antineoplastic

Biochem/physiol Actions

Mitoxantrone is a cytostatic anthracenedione that intercalates in DNA and increases the incidence of double-strand breaks by stabilizing the cleavable complex of topoisomerase II and DNA. Mitoxantrone also displays broad immunosuppressive activity inhibiting proliferation of all classes of lymphocytes and inducing apoptosis of antigen-presenting T cells. It used clinically as a chemotherapeutic agent against leukemias and solid tumors and as an immune system modulator in multiple sclerosis.

Clinical Use

Mitoxantrone is used in combination with other agents during the initial treatment of acute nonlymphocytic leukemia and hormone-refractory prostate cancer. Recent studies have shown that mitoxantrone also decreases the rate of relapse and disease progression in patients with multiple sclerosis. Although too toxic for use in patients with primary progressive disease, it is available for the treatment of chronic progressive, progressive relapsing, or deteriorating relapsing-remitting multiple sclerosis.

Metabolism

Mitoxantrone excretion primarily is biliary. Both the unchanged drug and inactive metabolites resulting from N-dealkylation, deamination, and oxidation of the resultant aldehyde to the carboxylic acid are observed. Both arms of the structure can be metabolized, leading to mono- or dicarboxylic acid metabolites, which are excreted as the glucuronide conjugate. The conjugated metabolites are an intense, dark blue in color and will result in blue-green urine.

InChI:InChI=1/C22H28N4O6.3ClH/c27-11-9-23-5-7-25-13-1-2-14(26-8-6-24-10-12-28)18-17(13)21(31)19-15(29)3-4-16(30)20(19)22(18)32;;;/h1-4,23-30H,5-12H2;3*1H

Upstream product

• 141-43-5 ethanolamine 
• 111228-29-6 5,8-dihydroxy-1,4-bis<(2-p-toluensulfonyloxyethyl)amino>anthracene-9,10-dione 
• 3179-90-6 5,8-dihydroxy-1,4-bis<<2-hydroxyethyl>amino>-9,10-anthracenedione 
• 65271-80-9 novantrone 

Relevant articles and documents

Novel anti-tumor compounds and application thereof

Mitoxantrone hydrochloride type [nu] and [omega] compounds are easier to prepare and more conducive to reducing energy consumption, have less hygroscopicity, better storage stability and the like, andare suitable for application in preparation of drugs for treatment or prevention of malignant lymphoma, breast cancer, acute leukemia, lung cancer, melanoma, soft tissue sarcoma, multiple myeloma, recurrent optic neuritis, multiple sclerosis and the like.

A new way of synthesizing 1,4-bis-substituted aminoalkylamino-anthraquinones

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1,4-Bis(substituted-amino)-5,8-dihydroxyanthraquinones and leuco bases thereof

This disclosure describes symmetrical 1,4-bis(substituted-amino)-5,8-dihydroxyanthraquinones useful as chelating agents and for inhibiting the growth of transplanted mouse tumors.