Structure-activity studies of antitumor agent irofulven (hydroxymethylacylfulvene) and analogues.
Many analogues of the antitumor agent irofulven have been readily prepared by replacing the allylic hydroxyl with a variety of nucleophiles. Analogues of acylfulvene (the precursor to irofulven) were also prepared by Michael reaction with acrolein. The toxicity of the analogues was determined, as well as preclinical antitumor activity. Several analogues exhibited good activity in mouse xenografts. Structural requirements for activity are discussed.
McMorris
T C
TC
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0506, USA. tmcmorris@ucsd.edu
Yu
J
J
Lira
R
R
Dawe
R
R
MacDonald
J R
JR
Waters
S J
SJ
Estes
L A
LA
Kelner
M J
MJ
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D018906:Antineoplastic Agents, Alkylating; D012717:Sesquiterpenes; C102714:irofulven