TY - JOUR
T1 - Synthesis and pharmacological evaluation of 4-iminothiazolidinones for inhibition of pi3 kinase
AU - Pinson, Jo Anne
AU - Schmidt-Kittler, Oleg
AU - Frazzetto, Mark
AU - Zheng, Zhaohua
AU - Jennings, Ian G.
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
AU - Chalmers, David K.
AU - Thompson, Philip E.
N1 - Funding Information:
J-A.P. is a recipient of an Australian Postgraduate Award (APA) Scholarship. This work was funded through the National Institutes of Health grants CA43460 and CA62924, the Virginia and D.K. Ludwig Fund for Cancer Research (USA), the Cancer Council Victoria no. 436708 and a National Health and Medical Research Council grant no. 545943 (Australia).
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
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U2 - 10.1071/CH12140
DO - 10.1071/CH12140
M3 - Article
C2 - 23997244
AN - SCOPUS:84867695912
SN - 0004-9425
VL - 65
SP - 1396
EP - 1404
JO - Australian Journal of Chemistry
JF - Australian Journal of Chemistry
IS - 10
ER -