6672. Nolatrexed

Nomenclature

CAS number: 147149-76-6
2-Amino-6-methyl-5-(4-pyridinylthio)-4(1H)-quinazolinone; 2-amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)quinazoline; 2-amino-6-methyl-5-(pyridin-4-ylsulfanyl)-3H-quinazolin-4-one.
C14H12N4OS; mol wt 284.34.
C 59.14%, H 4.25%, N 19.70%, O 5.63%, S 11.28%.

Description and references

Antifolate thymidylate synthase inhibitor. Prepn: S. E. Webber et al., WO 9320055; eidem, US 5707992 (1993, 1998 both to Agouron); S. E. Webber et al., J. Med. Chem. 36, 733 (1993). Solid-state properties: A. K. Dash, P. Tyle, J. Pharm. Sci. 85, 1123 (1996). Pharmacology: S. Webber et al., Cancer Chemother. Pharmacol. 37, 509 (1996). Clinical pharmacokinetics: I. Rafi et al., Clin. Cancer Res. 1, 1275 (1995). Clinical evaluation in hepatocellular carcinoma: K. Stuart et al., Cancer 86, 410 (1999).

Chemical structure

Properties

Tan solid, mp 301-302°.

Derivative

Dihydrochloride.

Nomenclature

CAS number: 152946-68-4
AG-337; Thymitaq (Zarix).
C14H12N4OS.2HCl; mol wt 357.26.
C 47.07%, H 3.95%, N 15.68%, O 4.48%, S 8.98%, Cl 19.85%.

Properties

Hygroscopic; occurs as a dihydrate. Sol in water. pKa 4.1; 5.9; 9.8. Partition coefficient (octanol/water) at 25°: 1.9. Upon heating, dehydrates and forms metastable, plate-like crystals, mp 213°. Recrystallizes at 261° into stable, needle-like crystals, mp 312° (dec).

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Antimetabolites; Folic Acid Analogs/Antagonists