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24584-09-6 molecular structure
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4-[(2S)-1-(3,5-dioxopiperazin-1-yl)propan-2-yl]piperazine-2,6-dione

ChemBase ID: 264
Molecular Formular: C11H16N4O4
Molecular Mass: 268.26914
Monoisotopic Mass: 268.11715501
SMILES and InChIs

SMILES:
O=C1NC(=O)CN([C@H](CN2CC(=O)NC(=O)C2)C)C1
Canonical SMILES:
O=C1NC(=O)CN(C1)C[C@@H](N1CC(=O)NC(=O)C1)C
InChI:
InChI=1S/C11H16N4O4/c1-7(15-5-10(18)13-11(19)6-15)2-14-3-8(16)12-9(17)4-14/h7H,2-6H2,1H3,(H,12,16,17)(H,13,18,19)/t7-/m0/s1
InChIKey:
BMKDZUISNHGIBY-ZETCQYMHSA-N

Cite this record

CBID:264 http://www.chembase.cn/molecule-264.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
4-[(2S)-1-(3,5-dioxopiperazin-1-yl)propan-2-yl]piperazine-2,6-dione
4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
IUPAC Traditional name
4-[(2S)-1-(3,5-dioxopiperazin-1-yl)propan-2-yl]piperazine-2,6-dione
dexrazoxane
Brand Name
Cardioxane
Dyzoxane
Eucardion
Razoxane
Razoxin
Tepirone
Troxozone
Zinecard
Synonyms
Dexrazoxano [INN-Spanish]
Dexrazoxanum [INN-Latin]
Dextrorazoxane
Desrazoxane
Razoxana [INN-Spanish]
Razoxanum [INN-Latin]
Icrf-187
Dexrazoxane
(+)-(S)-4,4′-Propylenedi-2,6-piperazinedione
(S)-(+)-1,2-Bis(3,5-dioxopiperazin-1-yl)propane
Cardioxane
NSC169780
Zinecard
Dexrazoxane
(S)-4,4'-(Propane-1,2-diyl)bis(piperazine-2,6-dione)
CAS Number
24584-09-6
MDL Number
MFCD00866449
PubChem SID
46505982
160963727
PubChem CID
71384

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 11.198792  H Acceptors
H Donor LogD (pH = 5.5) -2.6580358 
LogD (pH = 7.4) -2.6527913  Log P -2.652655 
Molar Refractivity 64.2532 cm3 Polarizability 25.298058 Å3
Polar Surface Area 98.82 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P -1.05  LOG S -1.41 
Solubility (Water) 1.04e+01 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Product Information Bioassay(PubChem)
Solubility
DMSO: >20 mg/mL expand Show data source
Sparingly soluble expand Show data source
Apperance
white to off-white powder expand Show data source
Hydrophobicity(logP)
-2.6 expand Show data source
European Hazard Symbols
Irritant Irritant (Xi) expand Show data source
UN Number
2811 expand Show data source
MSDS Link
Download expand Show data source
German water hazard class
3 expand Show data source
Hazard Class
6.1 expand Show data source
Packing Group
3 expand Show data source
Risk Statements
36/37/38 expand Show data source
Safety Statements
26-36 expand Show data source
GHS Pictograms
GHS07 expand Show data source
GHS Signal Word
Warning expand Show data source
GHS Hazard statements
H315-H319-H335 expand Show data source
GHS Precautionary statements
P261-P305 + P351 + P338 expand Show data source
RID/ADR
UN 2811 6.1/PG 3 expand Show data source
Storage Temperature
room temp expand Show data source
Purity
≥95% (HPLC) expand Show data source
95+% expand Show data source
97% expand Show data source
Empirical Formula (Hill Notation)
C11H16N4O4 expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Sigma Aldrich Sigma Aldrich
DrugBank - DB00380 external link
Item Information
Drug Groups approved
Description An antimitotic agent with immunosuppressive properties. Dexrazoxane, the (+)-enantiomorph of razoxane, provides cardioprotection against anthracycline toxicity. It appears to inhibit formation of a toxic iron-anthracycline complex. [PubChem]
The Food and Drug Administration has designated dexrazoxane as an orphan drug for use in the prevention or reduction in the incidence and severity of anthracycline-induced cardiomyopathy.
Indication For reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2 and would benefit from continued doxorubicin therapy. Also approved for the treatment of extravasation from intravenous anthracyclines.
Pharmacology Dexrazoxane is a cardioprotective agent for use in conjunction with doxorubicin indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage.
Toxicity Intraperitoneal, mouse LD10 = 500 mg/kg. Intravenous, dog LD10 = 2 gm/kg.
Affected Organisms
Humans and other mammals
Biotransformation Dexrazoxane is hydrolysed by the enzyme dihydropyrimidine amidohydrolase in the liver and kidney to active metabolites that are capable of binding to metal ions.
Absorption IV administration results in complete bioavailability.
Half Life 2.5 hours
Protein Binding Very low (< 2%)
Elimination Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of the 500 mg/m2 dose of dexrazoxane was excreted in the urine.
Distribution * 9 to 22.6 L/m^2
Clearance * 7.88 L/h/m2 [dose of 50 mg/m2 Doxorubicin and 500 mg/m2 Dexrazoxane]
* 6.25 L/h/m2 [dose of 60 mg/m2 Doxorubicin and 600 mg/m2 Dexrazoxane]
References
Hasinoff BB, Herman EH: Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol. 2007;7(2):140-4. [Pubmed]
Hasinoff BB: The use of dexrazoxane for the prevention of anthracycline extravasation injury. Expert Opin Investig Drugs. 2008 Feb;17(2):217-23. [Pubmed]
Kik K, Szmigiero L: [Dexrazoxane (ICRF-187)--a cardioprotectant and modulator of action of some anticancer drugs] Postepy Hig Med Dosw (Online). 2006;60:584-90. [Pubmed]
Weiss G, Loyevsky M, Gordeuk VR: Dexrazoxane (ICRF-187). Gen Pharmacol. 1999 Jan;32(1):155-8. [Pubmed]
Langer SW: Dexrazoxane for anthracycline extravasation. Expert Rev Anticancer Ther. 2007 Aug;7(8):1081-8. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com
Sigma Aldrich - D1446 external link
Biochem/physiol Actions
Dexrazoxane is a cardioprotective compound against anthracyclines. It functions by inhibiting topoisomerase II without inducing DNA strand breaks. Dexrazoxane is a + enantiomer of razoxane.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • Hasinoff BB, Herman EH: Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol. 2007;7(2):140-4. Pubmed
  • • Hasinoff BB: The use of dexrazoxane for the prevention of anthracycline extravasation injury. Expert Opin Investig Drugs. 2008 Feb;17(2):217-23. Pubmed
  • • Kik K, Szmigiero L: [Dexrazoxane (ICRF-187)--a cardioprotectant and modulator of action of some anticancer drugs] Postepy Hig Med Dosw (Online). 2006;60:584-90. Pubmed
  • • Langer SW: Dexrazoxane for anthracycline extravasation. Expert Rev Anticancer Ther. 2007 Aug;7(8):1081-8. Pubmed
  • • Weiss G, Loyevsky M, Gordeuk VR: Dexrazoxane (ICRF-187). Gen Pharmacol. 1999 Jan;32(1):155-8. Pubmed
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PATENTS

PATENTS

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