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Pixantrone

Product Name
Pixantrone
CAS No.
144510-96-3
Chemical Name
Pixantrone
Synonyms
CS-1359;pixantrone;Pixantrone, BBR 2778;BBR-2778;BBR2778;BBR 2778;Pixantrone diformate salt;6,9-Bis[(2-aminoethyl)amino]benz[g]isoquinoline-5,10-dione;6,9-bis((2-aminoethyl)amino)benzo(g)isoquinoline-5,10-dione;Benz[g]isoquinoline-5,10-dione, 6,9-bis[(2-aminoethyl)amino]-
CBNumber
CB71321822
Molecular Formula
C17H19N5O2
Formula Weight
325.37
MOL File
144510-96-3.mol
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Pixantrone Property

Melting point:
>173°C (dec.)
Boiling point:
650.0±55.0 °C(Predicted)
Density 
1.405
storage temp. 
Refrigerator
solubility 
DMSO (Slightly), Methanol (Slightly)
pka
9.34±0.10(Predicted)
form 
Solid
color 
Dark Blue to Very Dark Blue
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

American Custom Chemicals Corporation
Product number
API0005281
Product name
PIXANTRONE
Purity
95.00%
Packaging
1G
Price
$930.3
Updated
2021/12/16
AvaChem
Product number
2637B
Product name
Pixantrone
Packaging
5mg
Price
$45
Updated
2021/12/16
AvaChem
Product number
2637B
Product name
Pixantrone
Packaging
10mg
Price
$75
Updated
2021/12/16
CSNpharm
Product number
CSN12328
Product name
Pixantrone
Packaging
10mg
Price
$115
Updated
2021/12/16
AvaChem
Product number
2637B
Product name
Pixantrone
Packaging
25mg
Price
$145
Updated
2021/12/16
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Pixantrone Chemical Properties,Usage,Production

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.

Originator

University of Vermont (United States)

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.

Uses

anti-inflammatory and immunosuppressive glucocorticoid steroid

Definition

ChEBI: Pixantrone is a member of isoquinolines.

brand name

Pixuvri

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.

Synthesis

Pixantrone dimaleate, also known as BBR 2778, was originally synthesized by professors Krapcho and Hacker at the University of Vermont, and determination of in-vitro tumor cell cytotoxicity was co-identified by the Boehringer Mannheim Italia research center and the University of Vermont. After the merger of Boehringer Mannheim with La-Roche, Novuspharm, and Cell Therapeautics, Inc., pixantrone dimaleate has been developed and marketed by Cell Therapeutics, Inc.
The manufacturing scale synthesis of pixantrone dimaleate relies on several process modifications, from the original synthesis reported by Krapcho in 1994.169 This modified procedure has provided active pharmaceutical ingredient (API) in high purity (>99%) and is acceptable for use in pharmaceutical applications (the scheme). Beginning with pyridine 3,4-dicarboxylic acid (129), generation of the corresponding anhydride 130 proceeded in 76% yield upon treatment with refluxing Ac2O. Next, an AlCl3-promoted Friedel-Crafts reaction of 1,4-difluorobenzene (131) with 130 under reflux conditions provided a mixture of nicotinic acid isomers 132a/132b in 84% yield, which were carried directly to the next step. Cyclization with fuming H2SO4 yielded the desired difluorobenzoisoquinoline- dione core 133, which was further functionalized with ethylenediamine (134) to provide the free base of pixantrone. Subjection of the pixantrone free base to aqueous acetic anhydride and maleic acid provided pixantrone dimaleate (XX) in 92% yield over 3 steps.

Drug interactions

Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.
Live vaccines: risk of generalised infections - avoid.

Metabolism

Pixantrone may be metabolised in the liver and/or excreted in the bile. As metabolism appears to be limited, biliary excretion of unchanged pixantrone may be the major elimination pathway. Acetylated metabolites were pharmacologically inactive and metabolically stable. In human urine, the compound was mainly excreted unchanged, and very small amounts of phase I and phase II acetylated metabolites were found.

Pixantrone Preparation Products And Raw materials

Raw materials

Preparation Products

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Pixantrone Suppliers

Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
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China
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2922
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55
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
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China
ProdList
6005
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61
JinYan Chemicals(ShangHai) Co.,Ltd.
Tel
13817811078
Fax
86-021-50426522,50426273
Email
sales@jingyan-chemical.com
Country
China
ProdList
9976
Advantage
60
LGM Pharma
Tel
1-(800)-881-8210
Fax
615-250-9817
Email
inquiries@lgmpharma.com
Country
United States
ProdList
2123
Advantage
70
Chemsky (shanghai) International Co.,Ltd
Tel
021-50135380
Email
shchemsky@sina.com
Country
China
ProdList
15402
Advantage
60
ChemShuttle, Inc.
Tel
0510-83588313-802 18800520310;
Email
sales@chemshuttle.com
Country
China
ProdList
3002
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62
S.Z. PhyStandard Bio-Tech. Co., Ltd.
Tel
0755-83725681-603
Fax
+86 755 28094224
Country
China
ProdList
4496
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50
Shanghai potentpharm CO.,Ltd
Tel
13524892556
Fax
(86) 21 51969655, QQ: 263541193
Email
sales-cn@potentpharm.com
Country
China
ProdList
1011
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MedChemexpress LLC
Tel
021-58955995
Fax
609-228-5909
Email
sales@medchemexpress.cn
Country
United States
ProdList
4861
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58
Hubei XinyuanShun Chemical Co., Ltd.
Tel
13971561712, 13995564702, 027-50664929
Fax
027-50664927
Email
hbeixys2001@163.com
Country
China
ProdList
3120
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55
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View Lastest Price from Pixantrone manufacturers

Career Henan Chemical Co
Product
Pixantrone 144510-96-3
Price
US $1.00/KG
Min. Order
1G
Purity
98%
Supply Ability
100KG
Release date
2018-08-20

144510-96-3, PixantroneRelated Search:


  • 6,9-bis((2-aminoethyl)amino)benzo(g)isoquinoline-5,10-dione
  • pixantrone
  • 6,9-Bis[(2-aminoethyl)amino]benz[g]isoquinoline-5,10-dione
  • CS-1359
  • Pixantrone, BBR 2778
  • BBR-2778;BBR2778;BBR 2778
  • Benz[g]isoquinoline-5,10-dione, 6,9-bis[(2-aminoethyl)amino]-
  • Pixantrone diformate salt
  • 144510-96-3
  • APIs
  • Amines
  • Aromatics
  • Drug Analogues
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • API