Synthesis and pharmacological evaluation of 4-iminothiazolidinones for inhibition of pi3 kinase

Jo Anne Pinson, Oleg Schmidt-Kittler, Mark Frazzetto, Zhaohua Zheng, Ian G. Jennings, Kenneth W. Kinzler, Bert Vogelstein, David K. Chalmers, Philip E. Thompson

Research output: Contribution to journalArticle

Abstract

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 (US)
Pages (from-to)1396-1404
Number of pages9
JournalAustralian Journal of Chemistry
Volume65
Issue number10
DOIs
StatePublished - Oct 26 2012

ASJC Scopus subject areas

  • Chemistry(all)

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    Pinson, J. A., Schmidt-Kittler, O., Frazzetto, M., Zheng, Z., Jennings, I. G., Kinzler, K. W., Vogelstein, B., Chalmers, D. K., & Thompson, P. E. (2012). Synthesis and pharmacological evaluation of 4-iminothiazolidinones for inhibition of pi3 kinase. Australian Journal of Chemistry, 65(10), 1396-1404. https://doi.org/10.1071/CH12140