Description and references

Lipid soluble dihydrofolate reductase inhibitor. Prepn: E. M. Grivsky et al., J. Med. Chem. 23, 327 (1980); E. M. Grivsky et al., EP 21292 (1981 to Wellcome); E. M. Grivsky, US 4959474 (1990 to Burroughs Wellcome). Biochemistry and antitumor activity: D. S. Duch et al., Cancer Res. 42, 3987 (1982). Cytotoxicity: I. W. Taylor et al., ibid. 45, 978 (1985). Pharmacology and toxicology: C. W. Sigel et al., NCI Monogr. 5, 111 (1987). Antipneumocystis and antitoxoplasma activities: J. A. Kovacs et al., Antimicrob. Agents Chemother. 32, 430 (1988). HPLC determn in plasma: R. G. Foss, C. W. Sigel, J. Pharm. Sci. 71, 1176 (1982). Determn by protein binding assay in plasma: J. L. Woolley, Jr., et al., ibid. 78, 749 (1989). Crystal structure and conformational analysis: P. A. Sutton, V. Cody, J. Am. Chem. Soc. 110, 6219 (1988). Clinical pharmacology in children: P. C. Adamson et al., Cancer Res. 50, 4464 (1990). Clinical evaluation in lung cancer: M. G. Kris et al., Cancer Treat. Rep. 71, 763 (1987); in advanced squamous head and neck cancer: W.-C. Uen et al., Cancer 69, 1008 (1992).

Properties

Derivative