Water-soluble prodrugs of an Aurora kinase inhibitor

…, M Bui, E Delarosa, AD Fung, A Hashash, J Hau…

Index: Oslob, Johan D.; Heumann, Stacey A.; Yu, Chul H.; Allen, Darin A.; Baskaran, Subramanian; Bui, Minna; Delarosa, Erlie; Fung, Amy D.; Hashash, Ahmad; Hau, Jonathan; Ivy, Sheryl; Jacobs, Jeffrey W.; Lew, Willard; Maung, Jack; McDowell, Robert S.; Ritchie, Sean; Romanowski, Michael J.; Silverman, Jeffrey A.; Yang, Wenjin; Zhong, Min; Fuchs-Knotts, Tarra Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 5 p. 1409 - 1412

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Citation Number: 20

Abstract

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 ...