5092. Irofulven

Nomenclature

CAS number: 158440-71-2
(6′R)-6′-Hydroxy-3′-(hydroxymethyl)-2′,4′,6′-trimethylspiro[cyclopropane-1,5′-[5H]inden]-7′(6′H)-one; (hydroxymethyl)acylfulvene; HMAF; MGI-114; NSC-683863.
C15H18O3; mol wt 246.30.
C 73.15%, H 7.37%, O 19.49%.

Description and references

Semi-synthetic antitumor agent derived from illudin S, q.v. Inhibits DNA synthesis and induces apoptosis in tumor cells. Prepn: M. J. Kelner et al., US 5523490 (1996 to Univ. California); T. C. McMorris et al., J. Nat. Prod. 59, 896 (1996). Enantioselective synthesis: idem et al., J. Org. Chem. 69, 619 (2004). Effect on DNA integrity and apoptosis: J. M. Woynarowski et al., Biochem. Pharmacol. 54, 1181 (1997). Clinical pharmacokinetics and toxicology: J. Alexandre et al., Clin. Cancer Res. 10, 3377 (2004). Clinical evaluation in hormone-refractory prostate cancer: N. Senzer et al., Am. J. Clin. Oncol. 28, 36 (2005). Review: M. Baekelandt, Curr. Opin. Investig. Drugs 3, 1517-1526 (2002).

Chemical structure

Properties

Crystals from ether, mp 127-129°. [α]D25 639° (c = 0.096 in ethanol). Crystal density: 1.262 g/cm3. uv max (ethanol): 235, 330 nm (ε 15100, 9200) with tailing to 480 nm.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Alkaloids/Natural Products