Water-soluble prodrugs of an Aurora kinase inhibitor

Compound 1 (SNS-314) is a potent and selective Aurora kinase inhibitor that is currently in clinical trials in patients with advanced solid tumors. This communication describes the synthesis of prodrug derivatives of 1 with improved aqueous solubility profiles. In particular, phosphonooxymethyl-derived prodrug 2g has significantly enhanced solubility and is converted to the biologically active parent (1) following iv as well as po administration to rodents.

In vitro and in vivo properties of prodrug derivatives of the Aurora kinase inhibitor SNS-314 are described.Figure optionsDownload as PowerPoint slide