3437. Doxifluridine

Nomenclature

CAS number: 3094-09-5
5′-Deoxy-5-fluorouridine; 1-(β-d-5′-deoxyribofuranosyl)-5-fluorouracil; 5′-DFUR; 5′-dFUrd; Ro-21-9738; Flutron (Roche); Furtulon (Roche).
C9H11FN2O5; mol wt 246.19.
C 43.91%, H 4.50%, F 7.72%, N 11.38%, O 32.49%.

Description and references

Fluorinated pyrimidine nucleoside with cytostatic activity. Prepn: A. F. Cook, US 4071680 (1978 to Hoffmann-La Roche); H. Hrebabecky, J. Beranek, Nucleic Acids Res. 5, 1029 (1978); A. F. Cook et al., J. Med. Chem. 22, 1330 (1979). Stereospecific synthesis: J. Kiss et al., Helv. Chim. Acta 65, 1522 (1982). Mechanism of action studies: H.-R. Hartmann, A. Matter, Cancer Res. 42, 2412 (1982); R. D. Armstrong et al., Cancer Chemother. Pharmacol. 11, 102 (1983). Kinetics and metabolism in humans: J.-P. Sommadossi et al., Cancer Res. 43, 930 (1983). Clinical trials in colorectal carcinoma: R. Abele et al., J. Clin. Oncol. 1, 750 (1983); S. D. Fossa et al., Cancer Chemother. Pharmacol. 15, 161 (1985). Series of articles on animal toxicology: Yakuri to Chiryo 13, Suppl. 2, 221-430 (1985); acute toxicity: M. Shimizu et al., ibid. 209, C.A. 104, 14673z-14678e (1986). Evaluation of neurotoxicity in humans: M. S. Heier, S. D. Fossa, Acta Neurol. Scand. 73, 449 (1986).

Chemical structure

Properties

Crystals from ethyl acetate, mp 189-190° (Cook). Also reported as crystals from 2-propanol, mp 186-188° (Hrebabecky, Beranek); needles from methanol + ethyl acetate, mp 192-193° (Kiss). pKa 7.4. [α]D25 +18.4° (c = 0.419 in water). uv max (in methanol): 268-269 nm (ε 8550). LD50 (14 day) in mice or rats (mg/kg): >1000 i.v.: >2000 s.c.; in male, female mice, male, female rats (mg/kg): >5000, >5000, 3471, 3390 orally (Shimizu).

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Antimetabolites; Pyrimidine Analogs