title: Water-soluble prodrugs of an Aurora kinase inhibitor.
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 rodents.
authors.affiliation: Sunesis Pharmaceuticals, Inc., 395 Oyster Point Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Johan D
authors.initials: JD
authors.lastname: Oslob
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Heumann
authors.forename: Chul H
authors.initials: CH
authors.lastname: Yu
authors.forename: Darin A
authors.initials: DA
authors.lastname: Allen
authors.forename: Subramanian
authors.initials: S
authors.lastname: Baskaran
authors.forename: Minna
authors.initials: M
authors.lastname: Bui
authors.forename: Erlie
authors.initials: E
authors.lastname: Delarosa
authors.forename: Amy D
authors.initials: AD
authors.lastname: Fung
authors.forename: Ahmad
authors.initials: A
authors.lastname: Hashash
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hau
authors.forename: Sheryl
authors.initials: S
authors.lastname: Ivy
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Jacobs
authors.forename: Willard
authors.initials: W
authors.lastname: Lew
authors.forename: Jack
authors.initials: J
authors.lastname: Maung
authors.forename: Robert S
authors.initials: RS
authors.lastname: McDowell
authors.forename: Sean
authors.initials: S
authors.lastname: Ritchie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Romanowski
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Silverman
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.forename: Tarra
authors.initials: T
authors.lastname: Fuchs-Knotts
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D064127:Aurora Kinases; D008297:Male; D051379:Mice; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013844:Thiazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011355:Prodrugs; C532454:SNS 314; D013844:Thiazoles; D014867:Water; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases