Cyclophosphamide

Title: Cyclophosphamide
CAS Registry Number: 6055-19-2; 50-18-0 (anhydrous)
CAS Name: N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide monohydrate
Additional Names: 1-bis(2-chloroethyl)amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate; bis(2-chloroethyl)phosphamide cyclic propanolamide ester monohydrate; N,N-bis(b-chloroethyl)-N¢,O-propylenephosphoric acid ester diamide monohydrate; cyclophosphane; cytophosphane
Manufacturers' Codes: B-518
Trademarks: Cycloblastin (Pharmacia); Cyclostin (Pharmacia); Cytoxan (BMS); Endoxan (Baxter); Procytox (Baxter); Sendoxan (Baxter)
Molecular Formula: C7H15Cl2N2O2P.H2O
Molecular Weight: 279.10
Percent Composition: C 30.12%, H 6.14%, Cl 25.41%, N 10.04%, O 17.20%, P 11.10%
Literature References: Oxazaphosphine cytostatic agent; supresses B-cell activity and antibody formation. Prepn: H. Arnold, F. Bourseaux, Angew. Chem. 70, 539 (1958). Optical resolution study: T. Kawashima et al., J. Org. Chem. 43, 1111 (1978). Toxicology: A. G. Wheeler et al., Toxicol. Appl. Pharmacol. 4, 324 (1962). Book: D. L. Hill, A Review of Cyclophosphamide (Charles C Thomas, Springfield, 1975) 340 pp. Reviews of carcinogenicity studies: IARC Monographs 9, 135-156 (1975); of field trials as defleecing agent for sheep: M. H. Fahmy, Y. Moride, Anim. Breed. Abstr. 52, 7-19 (1984); of clinical toxicology: L. H. Fraiser et al., Drugs 42, 781-795 (1991); of mechanism of action and clinical use: O. M. Colvin, Curr. Pharmaceut. Design 5, 555-560 (1999); of analytical methods: M. Malet-Martino et al., ibid. 561-586; and metabolism: F. Baumann, R. Preiss, J. Chromatogr. B 764, 173-192 (2001).
Properties: mp 41-45° (Arnold); also reported as mp 47-49° (Hill). Soly in water: 40 g/l. Sol in alcohol, benzene, ethylene glycol, chloroform, dioxane; sparingly sol in ether and acetone. LD50 orally in mice, rats: 350, 94 mg/kg (Wheeler). Also marketed as the anhydrous form: crystals from ether, mp 51.5-52.5°.
Melting point: mp 41-45°; mp 47-49° ; mp 51.5-52.5°
Toxicity data: LD50 orally in mice, rats: 350, 94 mg/kg (Wheeler)
CAUTION: This substance is listed as a known human carcinogen: Report on Carcinogens, Eleventh Edition (PB2005-104914, 2004) p III-74.
Use: Defleecing agent for sheep.
Therap-Cat: Antineoplastic; immunosuppressant
Keywords: Antineoplastic; Alkylating Agents; Nitrogen Mustards.
Cyclopropane Cyclopropyl Methyl Ether Cyclorphan Cycloserine Cyclosporins

Cyclophosphamide
Cyclophosphamid.svg
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Systematic (IUPAC) name
(RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
Clinical data
Trade names Lyophilizedcytoxan
AHFS/Drugs.com monograph
MedlinePlus a682080
Pregnancy cat. D (AU) D (US)
Legal status Prescription only
Routes Oral, intravenous
Pharmacokinetic data
Bioavailability >75% (oral)
Protein binding >60%
Metabolism Hepatic
Half-life 3-12 hours
Excretion Renal
Identifiers
CAS number 50-18-0 YesY
ATC code L01AA01
DrugBank DB00531
ChemSpider 2804 YesY
UNII 6UXW23996M YesY
KEGG D07760 YesY
ChEBI CHEBI:4027 YesY
ChEMBL CHEMBL88 YesY
Chemical data
Formula C7H15Cl2N2O2P 
Mol. mass 261.086 g/mol
Physical data
Melt. point 2 °C (36 °F)
 YesY (what is this?)  (verify)

Cyclophosphamide (INN, trade names Endoxan, Cytoxan, Neosar, Procytox, Revimmune), also known as cytophosphane,[1] is a nitrogen mustard alkylating agent,[2] from the oxazaphosphinans group.

An alkylating agent adds an alkyl group (CnH2n+1) to DNA. It attaches the alkyl group to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring. This interferes with DNA replication by forming intrastrand and interstrand DNA crosslinks.

It is used to treat cancers and autoimmune disorders. As a prodrug, it is converted in the liver to active forms that have chemotherapeutic activity.

Cyclophosphamide has severe and life-threatening adverse effects, including acute myeloid leukemia, bladder cancer, hemorrhagic cystitis, and permanent infertility, especially at higher doses. For autoimmune diseases, doctors often substitute less-toxic methotrexate or azathioprine after an acute crisis.[3]