Description and references

Folic acid antagonist. Prepn: D. R. Seeger et al., J. Am. Chem. Soc. 71, 1753 (1949); J. M. Smith, D. B. Cosulich, US 2512572 (1950 to American Cyanamid). Metabolism: M. V. Freeman, J. Pharmacol. Exp. Ther. 122, 154 (1958); E. S. Henderson et al., Cancer Res. 25, 1008, 1018 (1965). Toxicity data: H. R. Scherf et al., Arzneim.-Forsch. 20, 1467 (1970). Comprehensive description: A. R. Chamberlin et al., Anal. Profiles Drug Subs. 5, 283-306 (1976). Review of metabolism and pharmacokinetics: W. E. Evans, Appl. Pharmacokinet. 1980, 518-548; of clinical pharmacology and toxicity: J. R. Bertino, Cancer Chemother. 3, 359-375 (1981); J. Jolivet et al., N. Engl. J. Med. 309, 1094-1104 (1983). Symposium on clinical experience in rheumatoid arthritis: J. Rheumatol. 12, Suppl. 12, 1-44 (1985). Review of use in leukemia: O. G. Jonsson, B. A. Kamen, Cancer Invest. 9, 53-60 (1991). Clinical trials in Crohn's disease: B. G. Feagan et al., N. Engl. J. Med. 332, 292 (1995); idem et al., ibid. 342, 1627 (2000). CE determn in blood: C.-Y. Kuo et al., J. Chromatogr. A 1014, 93 (2003). HPLC determin in blood: H. Li et al., J. Chromatogr. B 845, 164 (2007). Review of pulmonary toxicity: O. Lateef et al., Expert Opin. Drug Saf. 4, 723-730 (2005).

Derivative

Derivative