9721. Trimetrexate

Nomenclature

CAS number: 52128-35-5
5-Methyl-6-[[(3,4,5-trimethoxyphenyl)amino]methyl]-2,4-quinazolinediamine; 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline; TMQ; NSC-249008; JB-11; CI-898.
C19H23N5O3; mol wt 369.42.
C 61.77%, H 6.28%, N 18.96%, O 12.99%.

Description and references

Lipophilic dihydrofolate reductase inhibitor structurally related to methotrexate, q.v., with antimicrobial and antitumor activity. Prepn: E. F. Elslager, L. M. Werbel, GB 1345502 (1974 to Parke, Davis); E. F. Elslager et al., J. Med. Chem. 26, 1753 (1983); of water soluble salts: N. L. Colbry, EP 51415; idem, US 4376858 (1982, 1983 both to Warner-Lambert). In vitro antifolate activity and in vivo antitumor effect: J. R. Bertino et al., Biochem. Pharmacol. 28, 1983 (1979). Pharmacology: E. C. Weir et al., Cancer Res. 42, 1696 (1982); R. C. Jackson et al., Adv. Enzyme Regul. 22, 187 (1984). GC-MS determn in human plasma: P. L. Stetson, W. D. Ensminger, J. Chromatogr. 383, 69 (1986). Clinical evaluation with leucovorin vs Pneumocystis carinii in patients with AIDS: C. J. Allegra et al., N. Engl. J. Med. 317, 978 (1987). Review of pharmacology and clinical efficacy: J. T. Lin, J. R. Bertino, J. Clin. Oncol. 5, 2032-2040 (1987); P. J. O'Dwyer et al., NCI Monogr. 5, 105-109 (1987).

Chemical structure

Derivative

Monoacetate monohydrate.

Nomenclature

CAS number: 117381-09-6
C19H23N5O3.C2H4O2.H2O; mol wt 447.48.
C 56.37%, H 6.53%, N 15.65%, O 21.45%.

Properties

Crystals from aqueous acetic acid, mp 215-217°. Poorly sol in water. LD50 i.p. in mice: 175 mg/kg (Jackson).

Derivative

d-Glucuronate.

Nomenclature

CAS number: 82952-64-5
NSC-352122; Neutrexin (MedImmune).
C19H23N5O3.C6H10O7; mol wt 563.56.
C 53.28%, H 5.90%, N 12.43%, O 28.39%.

Properties

Tan colored solid. Soly in water: >50 mg/ml.

Therapeutic Category

Antineoplastic; antipneumocystis.

Keywords

Antineoplastic; Antimetabolites; Folic Acid Analogs/Antagonists