title: EB1627: a soluble prodrug of the potent anticancer cyanoguanidine CHS828.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, LEO Pharma, Industriparken 55, DK-2750 Ballerup, Denmark.
authors.forename: Ernst
authors.initials: E
authors.lastname: Binderup
authors.forename: Fredrik
authors.initials: F
authors.lastname: Björkling
authors.forename: Pernille Vig
authors.initials: PV
authors.lastname: Hjarnaa
authors.forename: Scilla
authors.initials: S
authors.lastname: Latini
authors.forename: Bodil
authors.initials: B
authors.lastname: Baltzer
authors.forename: Morten
authors.initials: M
authors.lastname: Carlsen
authors.forename: Lise
authors.initials: L
authors.lastname: Binderup
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs