890. Azacitidine

Nomenclature

CAS number: 320-67-2
4-Amino-1-β-d-ribofuranosyl-1,3,5-triazin-2(1H)-one; 5-azacytidine; 5-AzaC; ladakamycin; U-18496; NSC-102816; Mylosar (formerly); Vidaza (Pharmion).
C8H12N4O5; mol wt 244.20.
C 39.35%, H 4.95%, N 22.94%, O 32.76%.

Description and references

DNA methylation inhibitor; analog of the pyrimidine nucleoside, cytidine, q.v. Chemical synthesis: A. Piskala, F. Sorm, Collect. Czech. Chem. Commun. 29, 2060 (1964); M. W. Winkley, R. K. Robins, J. Org. Chem. 35, 491 (1970). Production by fermentation of Streptoverticillium ladakanus and activity: L. J. Hanka et al., Antimicrob. Agents Chemother. 1966, 619; M. E. Bergy, R. R. Herr, ibid. 625. HPLC determn in pharmaceutical prepns: L. D. Kissinger, N. L. Stemm, J. Chromatogr. 353, 309 (1986). Toxicology study: P. E. Palm, C. J. Kensler, U.S. Clearinghouse Fed. Sci. Tech. Inform. (PB-194791, 1970) 191 pp., C.A. 75, 33704j (1971). Review of clinical experience in acute nonlymphocytic leukemia: A. B. Glover et al., Cancer Treat. Rep. 71, 737-746 (1987); of mechanism of action: A. B. Glover, B. Leyland-Jones, ibid. 959-964. Review of carcinogenic risk: IARC Monographs 50, 47-63 (1990). Clinical efficacy in β-thalassemia: C. H. Lowrey, A. W. Nienhuis, N. Engl. J. Med. 329, 845 (1993); in myelodysplastic syndrome: L. R. Silverman et al., J. Clin. Oncol. 20, 2429 (2002); A. B. Kornblith et al., ibid. 2441.

Chemical structure

Properties

Crystals from aq ethanol, mp 235-237° (dec). [α]D26 +22.4° (c = 1 in water). uv max (water): 241 nm (ε 8767); (0.01N HCl): 249 nm (ε 3077); (0.01N KOH): 223 nm (ε 24200). Soly (mg/ml): 40 warm water, 14 cold water, 28 0.1N HCl, 43 0.1N NaOH, 52.7 DMSO, 1 acetone, 1 chloroform, 1 hexane. LD50 in mice (mg/kg): 115.9 i.p.; 572.3 orally (Palm, Kensler).

Caution

This substance is reasonably anticipated to be a human carcinogen: Report on Carcinogens, Eleventh Edition (PB2005-104914, 2004) p III-24.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Antimetabolites; Pyrimidine Analogs