EB1627: a soluble prodrug of the potent anticancer cyanoguanidine CHS828.
To overcome pharmacokinetic and solubility problems observed in early clinical trials with the potent anticancer compound CHS828, we synthesised a series of prodrugs with improved properties. The best compound obtained was EB1627, with a tetraethyleneglycol moiety attached to the parent drug via a carbonate linkage. This compound was found soluble enough to be given i.v. and the drug was rapidly released in vivo exerting a very potent inhibitory activity alone and in combination with known cytostatics (etoposide) in animal models in vivo.
Binderup
Ernst
E
Department of Medicinal Chemistry, LEO Pharma, Industriparken 55, DK-2750 Ballerup, Denmark.
Björkling
Fredrik
F
Hjarnaa
Pernille Vig
PV
Latini
Scilla
S
Baltzer
Bodil
B
Carlsen
Morten
M
Binderup
Lise
L
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D011355:Prodrugs