8099. Raltitrexed

Nomenclature

CAS number: 112887-68-0
N-[[5-[[(1,4-Dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]methylamino]-2-thienyl]carbonyl]-l-glutamic acid; N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl)-l-glutamic acid; ICI-D-1694; ZD-1694; Tomudex (AstraZeneca).
C21H22N4O6S; mol wt 458.49.
C 55.01%, H 4.84%, N 12.22%, O 20.94%, S 6.99%.

Description and references

Folate-based inhibitor of thymidylate synthase; rapidly and extensively metabolized to its more potent polyglutamate derivatives. Prepn: L. R. Hughes, EP 239362 (1987 to ICI; Natl. Res. Dev.); idem, US 4992550 (1991 to ICI); P. R. Marsham et al., J. Med. Chem. 34, 1594 (1991). Pharmacokinetics: D. I. Jodrell et al., Cancer Chemother. Pharmacol. 28, 331 (1991). HPLC determn of metabolites in cultured cells: W. Gibson et al., Biochem. Pharmacol. 45, 863 (1993). Review of clinical toxicology: S. J. Clarke et al., Adv. Exp. Med. Biol. 338, 601-604 (1993); of mechanism of action: A. L. Jackman et al., ibid. 339, 265-276. Historical development, pharmacology, and clinical evaluation: S. J. Clarke et al., ibid. 277-287; A. L. Jackman et al., Eur. J. Cancer 31A, 1277-1282 (1995).

Chemical structure

Properties

Pale yellow powder. Sol in water.

Derivative

Monohydrate.
C21H22N4O6S.H2O; mol wt 476.50.
C 52.93%, H 5.08%, N 11.76%, O 23.50%, S 6.73%.

Properties

mp 180-184°.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Antimetabolites; Folic Acid Analogs/Antagonists