Pixantrone

Base Information

• Chemical Name: Pixantrone
• CAS No.: 144510-96-3
• Molecular Formula: C17H19N5O2
• Molecular Weight: 325.37
• European Community (EC) Number: 680-661-5
• UNII: F5SXN2KNMR
• DSSTox Substance ID: DTXSID10162744
• Nikkaji Number: J580.321G
• Wikipedia: Pixantrone
• Wikidata: Q7199690
• NCI Thesaurus Code: C26663
• Metabolomics Workbench ID: 144690
• ChEMBL ID: CHEMBL167731
• Mol file: 144510-96-3.mol

Synonyms:5,8-bis((2-aminoethyl)amino)-2-aza-anthracene-9,10-dione;5,8-bis(2-aminoethylamino)-2-azaanthracene-9,10-dione;6,9-AEA-BIQDO;6,9-bis((2-aminoethyl)amino)benzo(g)isoquinoline-5,10-dione;BBR 2778;BBR-2778;BBR2778;pixantrone

Chemical Property of Pixantrone

Chemical Property:

• Vapor Pressure: 8.89E-17mmHg at 25°C
• Refractive Index: 1.728
• Boiling Point: 650 °C at 760 mmHg
• Flash Point: 346.9 °C
• PSA: 123.13000
• Density: 1.405 g/cm³
• LogP: 2.14480
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 1
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 325.15387487
• Heavy Atom Count: 24
• Complexity: 472

Purity/Quality:

98%,99%, ^*data from raw suppliers

Pixantrone ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CC(=C2C(=C1NCCN)C(=O)C3=C(C2=O)C=NC=C3)NCCN
• Recent ClinicalTrials: Study of Pixantrone in CD20+ Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma
• Recent EU Clinical Trials: A multicentre, phase II, open label, single arm study of pixantrone in patients with CD20-positive relapsed or refractory aggressive non-Hodgkin lymphoma treated with rituximab, ifosfamide and etoposide.
• Description: In May 2012, pixantrone was approved by the European Commission as a single agent for the treatment of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) in adult patients who have failed on at least two previous therapies. Pixantrone (also known as BBR- 2778) is an anthracycline analogue that was specifically designed to address the cardiotoxicity seen in earlier agents by replacement of a 1,4- dihydroxyanthracene-9,10-dione core with a benzoisoquinoline-5,10-dione ring system. Pixantrone inhibits topoisomerase II by intercalation with DNA and is also believed to form covalent adducts with the N-2 amino group of guanine via a formaldehyde aminal formed with the primary amino groups. Pixantrone is less cytotoxic than other anthracycline derivatives, but shows good antitumor activity in vivo in a variety of preclinical tumor models, including leukemia and lymphoma models. Pixantrone also demonstrated significantly reduced cardiotoxicity in preclinical models compared with the anthracyclines doxorubicin and mitroxantrone. Pixantrone was synthesized by Friedel–Crafts reaction of pyridine-3,4-dicarboxylic acid anhydride with 1,4-difluorobenzene to give a ketoacid that was cyclized to the tricyclic core by treatment with fuming sulfuric acid at 140℃. Reaction of the resulting 6,9-difluorobenzoisoquinoline-5-10-dione with ethylenediamine followed by careful pH adjustment and treatment with maleic acid gave pixantrone in good overall yield and purity.
• Uses: Pixantrone is an antineoplastic drug belonging to group of antitumor antibiotics. Pixantrone is an anlogue of Mitoxantrone (M373425) and is just as potent in the treatment of multiple sclerosis with fewer toxic effects on cardiac tissue. Studies suggest that Pixantrone significantly reduces amyloid beta (A beta(1-42)) neurotoxicity, a mechanism implicated in Alzheimer's disease. anti-inflammatory and immunosuppressive glucocorticoid steroid
• Clinical Use: Pixuvri (Pixantrone dimaleate) is a novel aza-anthracenedione derivative approved in Europe for the treatment of adult patients with non-Hodgkin B-cell lymphoma. It is also being pursued as a treatment for various cancers, and specifically as an alternative to other structurally-related drugs like mitoxantrone, employed for treatment of breast cancer, acute myeloid leukemia (AML), and non- Hodgkins lymphoma.Pixantrone dimaleate has been designed to maintain antitumor efficacy while decreasing highly cardiotoxic side effects observed during treatment with other related anti-tumor anthracenedione derivatives. Like many anthracenedione drugs, the mechanism of action for pixantrone dimaleate likely includes a number of pathways and processes, with studies suggesting intercalation into DNA and/or interference with DNA –Topoisomerase II activity, leading to subsequent protein associated-DNA strand breaks and eventually to cell death.
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine, increased risk of agranulocytosis. Live vaccines: risk of generalised infections - avoid.

Technology Process of Pixantrone

There total 6 articles about Pixantrone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

cinchomeronic anhydride (4664-08-8) → 6,9-bis{[2-(amino)ethyl]amino}benzo[g]isoquinoline-5,10-dione (144510-96-3)

Guidance literature:

Multi-step reaction with 2 steps

1: 1.) AlCl₃, 2.) f.H₂SO₄ / 1.) reflux, 22 h, 2.) from 135 to 140 deg C, 3 h

2: pyridine / 1.) RT, 12 h, 2.) 50 deg C, 2 h

With aluminium trichloride; sulfuric acid; In pyridine;

DOI:10.1021/jm00032a018

Reference yield:

3,4-pyridinecarboxylic acid (490-11-9) → 6,9-bis{[2-(amino)ethyl]amino}benzo[g]isoquinoline-5,10-dione (144510-96-3)

Guidance literature:

Multi-step reaction with 3 steps

1: 76 percent / acetic anhydride / 2 h / Heating

2: 1.) AlCl₃, 2.) f.H₂SO₄ / 1.) reflux, 22 h, 2.) from 135 to 140 deg C, 3 h

3: pyridine / 1.) RT, 12 h, 2.) 50 deg C, 2 h

With aluminium trichloride; sulfuric acid; acetic anhydride; In pyridine;

DOI:10.1021/jm00032a018

Reference yield:

6,9-dihydroxybenzo[g]isoquinoline-5,10-dione (4589-37-1) → 6,9-bis{[2-(amino)ethyl]amino}benzo[g]isoquinoline-5,10-dione (144510-96-3)

Guidance literature:

Multi-step reaction with 2 steps

1: 87 percent / 1.) NaOH, 2.) sodium dithionite / H₂O / 1 h / 70 °C

2: ethanol / 1 h / Heating

With sodium hydroxide; sodium dithionite; In ethanol; water;

DOI:10.1021/jm00032a018

upstream raw materials:

ethylenediamine

leuco-2-azaquinizarin

6,9-difluorobenzoisoquinoline-5,10-dione

cinchomeronic anhydride

Refernces

• 1、 -. "6,9 Bis(substituted-amino)benzo-[g]isoquinoline-5,10-diones". . . Retrieved 2008/06/13.