Water-soluble prodrugs of an Aurora kinase inhibitor

Autor:	Subramanian Baskaran, Jeffrey A. Silverman, Jack Maung, Stacey A. Heumann, Hashash Ahmad, Johan D. Oslob, Robert S. McDowell, Willard Lew, Minna Bui, Chul Yu, Michael J. Romanowski, Tarra Fuchs-Knotts, Jeffrey W. Jacobs, Jonathan Hau, Wenjin Yang, Darin Allen, Min Zhong, Amy D. Fung, Sheryl N. Ivy, Erlie Marie Delarosa, Sean Ritchie
Rok vydání:	2008
Předmět:	Male Clinical Biochemistry Aurora inhibitor Pharmaceutical Science Antineoplastic Agents Pharmacology Protein Serine-Threonine Kinases Biochemistry Rats Sprague-Dawley Mice Aurora Kinases Drug Discovery Aqueous solubility Animals In patient Prodrugs Solubility Molecular Biology Kinase Chemistry Phenylurea Compounds Organic Chemistry Water Biological activity Prodrug Rats Thiazoles Water soluble Molecular Medicine
Zdroj:	Bioorganicmedicinal chemistry letters. 19(5)
ISSN:	1464-3405
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5bec73e8f2a8e0074d6d3e16c6a29438 https://pubmed.ncbi.nlm.nih.gov/19186057 Zobrazit plný text záznamu Full Text from ScienceDirect