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
AU - Kinzler, Ken
AU - Vogelstein, Bert
AU - Chalmers, David Kenneth
AU - Thompson, Philip
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.
UR - http://www.publish.csiro.au/journals/ajc
U2 - 10.1071/CH12140
DO - 10.1071/CH12140
M3 - Article
SN - 0004-9425
VL - 65
SP - 1396
EP - 1404
JO - Australian Journal of Chemistry
JF - Australian Journal of Chemistry
IS - 10
ER -