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3778-73-2 molecular structure
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3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-1,3,2λ5-oxazaphosphinan-2-one

ChemBase ID: 1052
Molecular Formular: C7H15Cl2N2O2P
Molecular Mass: 261.085961
Monoisotopic Mass: 260.02481972
SMILES and InChIs

SMILES:
ClCCN1P(=O)(OCCC1)NCCCl
Canonical SMILES:
ClCCNP1(=O)OCCCN1CCCl
InChI:
InChI=1S/C7H15Cl2N2O2P/c8-2-4-10-14(12)11(6-3-9)5-1-7-13-14/h1-7H2,(H,10,12)
InChIKey:
HOMGKSMUEGBAAB-UHFFFAOYSA-N

Cite this record

CBID:1052 http://www.chembase.cn/molecule-1052.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-1,3,2λ5-oxazaphosphinan-2-one
3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-1,3,2$l^{5}-oxazaphosphinan-2-one
(2S)-3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-1,3,2λ5-oxazaphosphinan-2-one
IUPAC Traditional name
ifosfamide
(2S)-3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-1,3,2λ5-oxazaphosphinan-2-one
Brand Name
Cyfos
Holoxan 1000
IFEX
Ifex/Mesnex Kit
Ifosfamide/Mesna Kit
Isoendoxan
Mitoxana
Naxamide
Synonyms
N,3-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine-2-oxide
Ifosfamide
Asta Z 4942
Ifosfamid
Ifosfamide Sterile
Ifsofamide
Iphosphamid
Iphosphamide
Isophosphamide
Isofosfamide
I-Phosphamide
Ifosphamide
Ifosfamide
Mitoxana
Ifex
(S)-3-(2-chloroethyl)-2-((2-chloroethyl)amino)-1,3,2-oxazaphosphinane 2-oxide
Dexifosfamide
N,3-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-Oxide
A 4942
Cyfos
Holoxan
Ifomide
MJF 9325
NSC 109724
Naxamide
Isophosphamide
CAS Number
3778-73-2
66849-34-1
EC Number
223-237-3
MDL Number
MFCD00057374
PubChem SID
46508335
160964515
PubChem CID
3690

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 13.238064  H Acceptors
H Donor LogD (pH = 5.5) 0.09654586 
LogD (pH = 7.4) 0.096547104  Log P 0.096547686 
Molar Refractivity 58.4781 cm3 Polarizability 23.373835 Å3
Polar Surface Area 41.57 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P 0.57  LOG S -1.24 
Solubility (Water) 1.50e+01 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
3780 mg/L expand Show data source
DMSO expand Show data source
Methanol expand Show data source
Water expand Show data source
Apperance
White to Off-White Solid expand Show data source
Melting Point
39-41°C expand Show data source
Hydrophobicity(logP)
0.8 expand Show data source
Storage Condition
-20°C expand Show data source
-20°C Freezer, Under Inert Atmosphere expand Show data source
RTECS
RP6050000 expand Show data source
European Hazard Symbols
Toxic Toxic (T) expand Show data source
UN Number
2811 expand Show data source
MSDS Link
Download expand Show data source
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
25-36 expand Show data source
Safety Statements
26-45 expand Show data source
GHS Pictograms
GHS06 expand Show data source
GHS Signal Word
Danger expand Show data source
GHS Hazard statements
H301-H319 expand Show data source
GHS Precautionary statements
P301 + P310-P305 + P351 + P338 expand Show data source
Personal Protective Equipment
Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges expand Show data source
RID/ADR
UN 2811 6.1/PG 3 expand Show data source
Storage Temperature
2-8°C expand Show data source
Target
DNA/RNA synthesis expand Show data source
Mechanism of Action
Alkylating agent in cancer therapy expand Show data source
Purity
≥98% expand Show data source
97% expand Show data source
Salt Data
Free Base expand Show data source
Certificate of Analysis
Download expand Show data source
Application(s)
Antileukaemic expand Show data source
Antineoplastic expand Show data source
Immunosuppressant expand Show data source
Shipped in
wet ice expand Show data source
Empirical Formula (Hill Notation)
C7H15Cl2N2O2P expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich TRC TRC
DrugBank - DB01181 external link
Item Information
Drug Groups approved
Description Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [PubChem]
Indication Used as a component of various chemotherapeutic regimens as third-line therapy for recurrent or refractory germ cell testicular cancer. Also used as a component of various chemotherapeutic regimens for the treatment of cervical cancer, as well as in conjunction with surgery and/or radiation therapy in the treatment of various soft tissue sarcomas. Other indications include treatment of osteosarcoma, bladder cancer, ovarian cancer. small cell lung cancer, and non-Hodgkin's lymphoma.
Pharmacology Ifosfamide requires activation by microsomal liver enzymes to active metabolites in order to exert its cytotoxic effects. Activation occurs by hydroxylation at the ring carbon atom 4 to form the unstable intermediate 4-hydroxyifosfamide. This metabolite than rapidly degrades to the stable urinary metabolite 4-ketoifosfamide. The stable urinary metabolite, 4-carboxyifosfamide, is formed upon opening of the ring. These urinary metabolites have not been found to be cytotoxic. N, N-bis (2-chloroethyl)-phosphoric acid diamide (ifosphoramide) and acrolein are also found. The major urinary metabolites, dechloroethyl ifosfamide and dechloroethyl cyclophosphamide, are formed upon enzymatic oxidation of the chloroethyl side chains and subsequent dealkylation. It is the alkylated metabolites of ifosfamide that have been shown to interact with DNA. Ifosfamide is cycle-phase nonspecific.
Toxicity LD50 (mouse) = 390-1005 mg/kg, LD50 (rat) = 150-190 mg/kg. Side effects include nausea, vomiting and myelosuppression. Toxic effects include central nervous system toxicity (confusion, hallucinations) and urotoxic effects (cystitis, blood in urine).
Affected Organisms
Humans and other mammals
Biotransformation Primarily hepatic
Half Life 7-15 hours
Protein Binding Minimal
Elimination Ifosfamide is extensively metabolized in humans and the metabolic pathways appear to be saturated at high doses. After administration of doses of 5 g/m2 of 14C-labeled ifosfamide, from 70% to 86% of the dosed radioactivity was recovered in the urine, with about 61% of the dose excreted as parent compound. At doses of 1.6–2.4 g/m2 only 12% to 18% of the dose was excreted in the urine as unchanged drug within 72 hours.
References
Furlanut M, Franceschi L: Pharmacology of ifosfamide. Oncology. 2003;65 Suppl 2:2-6. [Pubmed]
Fleming RA: An overview of cyclophosphamide and ifosfamide pharmacology. Pharmacotherapy. 1997 Sep-Oct;17(5 Pt 2):146S-154S. [Pubmed]
Wagner T: Ifosfamide clinical pharmacokinetics. Clin Pharmacokinet. 1994 Jun;26(6):439-56. [Pubmed]
Allen LM, Creaven PJ, Nelson RL: Studies on the human pharmacokinetics of isophosphamide (NSC-109724). Cancer Treat Rep. 1976 Apr;60(4):451-8. [Pubmed]
Brade WP, Herdrich K, Varini M: Ifosfamide--pharmacology, safety and therapeutic potential. Cancer Treat Rev. 1985 Mar;12(1):1-47. [Pubmed]
Zalupski M, Baker LH: Ifosfamide. J Natl Cancer Inst. 1988 Jun 15;80(8):556-66. [Pubmed]
Willits I, Price L, Parry A, Tilby MJ, Ford D, Cholerton S, Pearson AD, Boddy AV: Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35. [Pubmed]
Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [Pubmed]
Schoenike SE, Dana WJ: Ifosfamide and mesna. Clin Pharm. 1990 Mar;9(3):179-91. [Pubmed]
Dechant KL, Brogden RN, Pilkington T, Faulds D: Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. Drugs. 1991 Sep;42(3):428-67. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com
Selleck Chemicals - S1302 external link
Research Area: Cancer
Biological Activity:
Ifosfamide is a nitrogen mustard alkylating agent used in the treatment of cancer. It is given as a treatment for a variety of cancers. [1]
Sigma Aldrich - I4909 external link
Biochem/physiol Actions
Ifosfamide is a nitrogen mustard compound that is a structural isomer of cyclophosphamide. Ifosfamide is a prodrug that must be transformed by cytochrome P450 to the biologically active component. It is used as an antineoplastic agent in cancer chemotherapy, but ifosfamide is more likely to cause renal toxicity than cyclophosphamide.
Toronto Research Chemicals - I265000 external link
A cytostatic agent, related structurally to cyclophosphamide.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • Fleming RA: An overview of cyclophosphamide and ifosfamide pharmacology. Pharmacotherapy. 1997 Sep-Oct;17(5 Pt 2):146S-154S. Pubmed
  • • Wagner T: Ifosfamide clinical pharmacokinetics. Clin Pharmacokinet. 1994 Jun;26(6):439-56. Pubmed
  • • Allen LM, Creaven PJ, Nelson RL: Studies on the human pharmacokinetics of isophosphamide (NSC-109724). Cancer Treat Rep. 1976 Apr;60(4):451-8. Pubmed
  • • Brade WP, Herdrich K, Varini M: Ifosfamide--pharmacology, safety and therapeutic potential. Cancer Treat Rev. 1985 Mar;12(1):1-47. Pubmed
  • • Zalupski M, Baker LH: Ifosfamide. J Natl Cancer Inst. 1988 Jun 15;80(8):556-66. Pubmed
  • • Willits I, Price L, Parry A, Tilby MJ, Ford D, Cholerton S, Pearson AD, Boddy AV: Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35. Pubmed
  • • Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. Pubmed
  • • Schoenike SE, Dana WJ: Ifosfamide and mesna. Clin Pharm. 1990 Mar;9(3):179-91. Pubmed
  • • Dechant KL, Brogden RN, Pilkington T, Faulds D: Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. Drugs. 1991 Sep;42(3):428-67. Pubmed
  • • Furlanut M, Franceschi L: Pharmacology of ifosfamide. Oncology. 2003;65 Suppl 2:2-6. Pubmed
  • • http://en.wikipedia.org/wiki/Ifosfamide
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