Synthesis and pharmacological evaluation of 4-iminothiazolidinones for inhibition of PI3 kinase

Jo-Anne Pinson, Oleg Schmidt-Kittler, Mark Frazzetto, Zhaohua Zheng, Ian Jennings, Ken Kinzler, Bert Vogelstein, David Kenneth Chalmers, Philip Thompson

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The thiazolidinedione, compound 1, has previously shown pan-inhibition of the phosphoinositide 3-kinase (PI3K) class I isoforms. We hypothesized the derivatization of the thiazolidinedione core of compound 1 could introduce isoform selectivity. We report the synthesis, characterization, and inhibitory activity of a novel series of 4-iminothiazolidin-2-ones for inhibition of the class I PI3K isoforms. Their synthesis was successfully achieved by multiple pathways described in this paper. Initial in vitro data of 28 analogues demonstrated poor inhibition of all class I PI3K isoforms. However, we identified an alternate target, the phosphodiesterases, and present preliminary screening results showing improved inhibitory activity.
Original languageEnglish
Pages (from-to)1396 - 1404
Number of pages9
JournalAustralian Journal of Chemistry
Issue number10
Publication statusPublished - 2012

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