404. Amifostine

Nomenclature

CAS number: 20537-88-6
2-[(3-Aminopropyl)amino]ethanethiol 1-(dihydrogen phosphate); phosphorothioic acid S-[2-[(3-aminopropyl)amino]ethyl] ester; aminopropylaminoethyl thiophosphate; ethiofos; gammaphos; SAPEP; NSC-296961; WR-2721; YM-08310; Ethyol (U.S. Bioscience).
C5H15N2O3PS; mol wt 214.22.
C 28.03%, H 7.06%, N 13.08%, O 22.41%, P 14.46%, S 14.97%.

Description and references

Thiophosphate derivative of cysteamine, q.v.; provides normal cells with selective protection against the toxic effects of cancer chemotherapy and radiation treatment. Prepn of monohydrate: J. R. Piper et al., J. Med. Chem. 12, 236 (1969); J. R. Piper, T. P. Johnston, US 3892824 (1975 to Southern Res. Inst.). Differential radioprotective activity: J. M. Yuhas, J. B. Storer, J. Natl. Cancer Inst. 42, 331 (1969). Mechanism of action study: G. D. Smoluk et al., Cancer Res. 48, 3641 (1988). Bioavailability: L. Fleckenstein et al., Pharmacol. Ther. 39, 203 (1988). Clinical pharmacokinetics: L. M. Shaw et al., ibid. 195. HPLC determn in plasma: N. F. Swynnerton et al., Int. J. Radiat. Oncol. Biol. Phys. 12, 1495 (1986). Review of development as radioprotector: D. Q. Brown et al., Pharmacol. Ther. 39, 157-168 (1988); of role in chemotherapy: R. L. Capizzi et al., Cancer 72, 3495-3501 (1993); M. Treskes, W. J. M. van der Vijgh, Cancer Chemother. Pharmacol. 33, 93-106 (1993).

Chemical structure

Derivative

Monohydrate.

Nomenclature

CAS number: 63717-27-1

Properties

White solid from methanol/ether, mp 160-161° (dec). LD50 in mice (mg/kg): 700 i.p. (Piper, Johnston).

Derivative

Trihydrate.

Nomenclature

CAS number: 112901-68-5

Properties

Soly in water: >9 g/100 ml. pKa1 <2.0; pKa2 4.2; pKa3 9.0; pKa4 11.7.

Therapeutic Category

Radioprotective agent.

Keywords

Antineoplastic Adjunct; Radioprotective