Ifosfamid

Bezeichnung:Ifosfamid

CAS-Nr3778-73-2

Englisch Name:Ifosfamide

CBNumberCB7489350

SummenformelC7H15Cl2N2O2P

Molgewicht261.09

MOL-Datei3778-73-2.mol

Synonyma

Ifosfamid

Ifosfamid physikalisch-chemischer Eigenschaften

Schmelzpunkt	48°C
Siedepunkt	336.1±52.0 °C(Predicted)
Dichte	1.33±0.1 g/cm3(Predicted)
storage temp.	Inert atmosphere,2-8°C
Löslichkeit	DMF:50.0(Max Conc. mg/mL);191.51(Max Conc. mM) DMSO:44.0(Max Conc. mg/mL);168.53(Max Conc. mM) Ethanol:51.0(Max Conc. mg/mL);195.34(Max Conc. mM) PBS (pH 7.2):10.0(Max Conc. mg/mL);38.3(Max Conc. mM) Water:52.0(Max Conc. mg/mL);199.17(Max Conc. mM)
pka	1.44±0.20(Predicted)
Aggregatzustand	Solid
Farbe	White to off-white
CAS Datenbank	3778-73-2(CAS DataBase Reference)
IARC	3 (Vol. 26, Sup 7) 1987
EPA chemische Informationen	Isophosphamide (3778-73-2)

Sicherheit

Kennzeichnung gefährlicher	T
R-Sätze:	25-36
S-Sätze:	26-45
RIDADR	3249
WGK Germany	3
RTECS-Nr.	RP6050000
HazardClass	6.1(b)
PackingGroup	III
HS Code	29349990
Giftige Stoffe Daten	3778-73-2(Hazardous Substances Data)
Toxizität	LD50 in rats (mg/kg): 160 i.p. (Arnold, 1973); also reported as 150 i.p. (Brock)

Gefahreninformationscode (GHS)

Ifosfamide Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R25:Giftig beim Verschlucken.
R36:Reizt die Augen.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
Chemische Eigenschaften
Crystalline Solid
Originator
Holoxan,Lucien,France,1976
Verwenden
Ifosphamide USP (Ifex)is used to treat germ cell testicular cancer; used in combination with mesna.
Verwenden
antibacterial
Verwenden
A cytostatic agent, related structurally to cyclophosphamide
Indications
Ifosfamide (Ifex) is an analogue of cyclophosphamide that requires metabolic activation to form 4-hydroxyifosfamide. In general, the metabolism, serum half-life, and excretion of ifosfamide are similar to those of cyclophosphamide.
Ifosfamide is active against a broad spectrum of tumors, including germ cell cancers of the testis, lymphomas, sarcomas, and carcinomas of the lung, breast, and ovary. It is thought to be more active than cyclophosphamide in germ cell cancers and sarcomas.
Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. It also may produce alopecia, nausea, vomiting, infertility, and second tumors, particularly acute leukemias. Neurological symptoms including confusion, somnolence, and hallucinations have also been reported. It is recommended that ifosfamide be coadministered with the thiol compound mesna (Mesnex) to avoid hemorrhagic cystitis.
Definition
ChEBI: The simplest member of the class of ifosfamides that is 1,3,2-oxazaphosphinan-2-amine 2-oxide substituted by 2-chloroethyl groups on both the nitrogen atoms respectively. It is a nitrogen mustard alkylating agent used in the treatment of advanced breast c ncer.
Manufacturing Process
127.6 g (1.1 mols) of N-(2-chloroethyl)-amine hydrochloride are suspended in a solution of 218 g (1 mol) of N-(2-chloroethyl)-N,O-propylene phosphoric acid ester amide monochloride in 600 cc of methylene dichloride, and 212 g of triethylamine are added thereto dropwise with stirring. The reaction mixture is heated to boiling by the reaction heat. After termination of the addition, the reaction mixture is heated to boiling for another 2 hours. Thereafter, it is cooled to room temperature and the precipitated triethylamine hydrochloride is separated by filtration with suction. The filtrate is extracted with about 60cc of dilute hydrochloric acid (pH 3), then twice with about 60 cc of water, thereafter with about 60 cc of dilute soda lye and finally twice with about 60 cc of water. After drying over anhydrous sodium sulfate, methylene dichloride is distilled off under normal pressure. The oily residue is dried in a vacuum and thereafter extracted in a perforator with 500 cc of anhydrous ether. The oily extract crystallizes upon inoculation and standing in an ice box. After standing for several hours, the precipitate is filtered off, washed with a small amount of cold ether and dried in a vacuum at room temperature. Yield: 185 g (71% of the theoretical). This material is also identified as 3-(2- chloroethyl)-2-(2-chloroethylamino)-tetrahydro-2H-1,3,2-oxazaphosphorin-2- oxide; generic name: ifosfamide. F.P.: 39°C to 41°C.
Trademarks
Ifex (Bristol-Myers Squibb).
Therapeutic Function
Antineoplastic
Allgemeine Beschreibung
Ifosfamide is available in 1- and 3-g vials for IV administrationas Food and Drug Administration (FDA)-approvedthird-line therapy in the treatment of testicular cancer. It has also been utilized (although not FDA approved) in the treatmentof a wide variety of cancers including Hodgkin’s andnon-Hodgkin’s lymphoma, soft tissue sarcoma, germ celltumors, small cell lung cancer, non–small cell lung cancer(NSCLC), cancers of the head and neck, bladder cancer, cervicalcancer, and Ewing sarcoma. Coadministration ofmesna is recommended. The mechanisms of resistance areidentical to those seen with cyclophosphamide. The drug iswidely distributed with a low extent of protein binding(20%). Metabolism primarily by CYP3A4/5 and CYP2B6 isrequired for activation of the compound. Theagent is administered as the racemic mixture as a result ofthe presence of the chiral phosphorus atom, and differentialmetabolism of the R- and S-isomers has been observed. Incontrast to cyclophosphamide, there is a greater amount ofdeactivation of the agent by N-dechloroethylation and subsequentlymore chloroacetaldehyde is produced, which mayresult in a greater amount of neurotoxicity and nephrotoxicitythan seen with cyclophosphamide. The N-dechloroethylatedmetabolites are the predominate species seen in theplasma. The parent and metabolites are eliminated inthe urine with an elimination half-life of 3 to 10 hours. Themajor components found in the urine are the dechlorethylatedmetabolites. Dose-limiting toxicities include myelosuppressionand bladder toxicity. Other adverse effectsinclude nausea, alopecia, amenorrhea, inappropriate secretionof antidiuretic hormone, as well as the production ofsecondary cancers. Neurotoxicity, which is associated withthe production of chloroacetaldehyde presents as confusion,seizure, weakness, and hallucination, and coma may occur.
Clinical Use
Ifosamide currently is used as “third-line” therapy against testicular cancer, although it also has shown activity in a number of solid tumors and hematologic cancers.
Nebenwirkungen
Patients on ifosfamide (but not cyclophosphamide) commonly exhibit central nervous system (CNS) toxicity. In severe forms, CNS depression can progress to coma and death.
Synthese
Ifosfamide, 3-(2-chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-2H-1,3,2- oxazaphosphorin-2-oxide (30.2.1.17), which is viewed as an isomeric compound of cyclophosphamide (30.2.1.15) and which is analogous in terms of action, is made by reacting N-(2-chloroethyl)-N-(3-hydroxypropyl)amine with phosphorous oxychloride, giving 3-(2-chloroethyl)-2-chlorotetrahydro-2H-1,3,2-oxazaphosphorin-2-oxide (30.2.1.16), which is reacted with N-(2-chloroethyl)amine, forming the desired ifosfamide (30.2.1.17).
Veterinary Drugs and Treatments
In small animals, ifosfamide may be of benefit as part of treatment protocols for a variety of neoplasms. Treatment of lymphomas and soft tissue sarcomas with ifosfamide in dogs and cats has been investigated to some extent; some efficacy has been demonstrated.
In humans, ifosfamide is used in various treatment protocols for testicular neoplasms, bone and soft tissue sarcomas, bladder cancer, lung cancer, cervical cancer, ovarian cancer, and some types of lymphomas.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Anticoagulants: possibly enhanced effect of coumarins.
Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis).
Stoffwechsel
The pharmacokinetics of ifosfamide are reported to exhibit considerable inter-individual variation. It is a prodrug that is extensively metabolised, chiefly by cytochrome P450 isoenzymes CYP3A4 and CYP2B6 in the liver, to both active and inactive alkylating metabolites; there is some evidence that metabolism is saturated at very high doses. After repeated doses (fractionated therapy) there is a decrease in the elimination half-life, apparently due to auto-induction of metabolism. It is excreted largely in urine, as unchanged drug (80%) and metabolites.

Ifosfamide Upstream-Materialien And Downstream Produkte

Ifosfamid Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

3778-73-2, Ifosfamide Verwandte Suche:

Send Inquriy