9788. Troxacitabine

Nomenclature

CAS number: 145918-75-8
4-Amino-1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]-2(1H)-pyrimidinone; (-)-2′-deoxy-3′-oxacytidine; β-l-(-) dioxolane cytidine; (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]cytosine; l-OddC; (-)-BCH-204; BCH-4556; Troxatyl (Shire Biochem).
C8H11N3O4; mol wt 213.19.
C 45.07%, H 5.20%, N 19.71%, O 30.02%.

Description and references

Synthetic nucleoside analog with stereochemically unnatural β-l configuration. Prepn: Y.-C. Cheng et al., WO 9218517 (1992 to Yale Univ. and Univ. Georgia Res. Found.); B. R. Belleau et al., Tetrahedron Lett. 33, 6949 (1992); H. O. Kim et al., J. Med. Chem. 36, 519 (1993). Resolution of enantiomers: M. P. DiMarco et al., J. Chromatogr. 645, 107 (1993). Structure activity study: T. S. Mansour et al., Nucleosides Nucleotides 14, 627 (1995). Clinical pharmacokinetics: J. S. deBono et al. J. Clin. Oncol. 20, 96 (2001). Population pharmacokinetics: C. K. K. Lee et al., Clin. Cancer Res. 12, 2158 (2006). Clinical evaluation in refractory leukemia: F. J. Giles et al., ibid. 20, 656 (2002); in imatinib-resistant chronic myelogenous leukemia: idem et al., Leuk. Res. 27, 1091 (2003); in pancreatic cancer: R. Lapointe et al., Ann. Oncol. 16, 289 (2005). Review of pharmacology and clinical development: idem, Expert Rev. Anticancer Ther. 2, 261-266 (2002); G. Ecker, Curr. Opin. Investig. Drugs 3, 1533-1538 (2002).

Chemical structure

Properties

mp 176-177°. [α]D25 -38.33° (c = 0.43 in MeOH). uv max (water): 270.0 (pH 7), 278.0 (pH 2), 269.0 (pH 11) ( ε 7770, 11970, 8380).

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Antimetabolites; Pyrimidine Analogs