2747. Cyclophosphamide

Nomenclature

CAS number: 6055-19-2; 50-18-0 (anhydrous)
N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide monohydrate; 1-bis(2-chloroethyl)amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate; bis(2-chloroethyl)phosphamide cyclic propanolamide ester monohydrate; N,N-bis(β-chloroethyl)-N′,O-propylenephosphoric acid ester diamide monohydrate; cyclophosphane; cytophosphane; B-518; Cycloblastin (Pharmacia); Cyclostin (Pharmacia); Cytoxan (BMS); Endoxan (Baxter); Procytox (Baxter); Sendoxan (Baxter).
C7H15Cl2N2O2P.H2O; mol wt 279.10.
C 30.12%, H 6.14%, Cl 25.41%, N 10.04%, O 17.20%, P 11.10%.

Description and 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. Pharm. Des. 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); of clinical pharmacokinetics: M. E. de Jonge et al.,Clin. Pharmacokinet. 44, 1135-1164 (2005).

Chemical structure

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°.

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.

Therapeutic Category

Antineoplastic; immunosuppressant

Therapeutic Category (Veterinary)

Antineoplastic; immunosuppressant.

Keywords

Antineoplastic; Alkylating Agents; Nitrogen Mustards