Synthesis of new pyridothienopyrimidinone and pyridothienotriazolopyrimidine derivatives as pim-1 inhibitors

<p>Three series of 2-arylpyridothieno[3,2-<i>d</i>]pyrimidin-4-ones <b>3a–j</b>, pyridothienotriazolopyrimidines <b>6–8</b> and 4-imino-pyridothieno[3,2-<i>d</i>]pyrimidines <b>9a,b</b> were prepared to improve the pim-1 inhibitory activity of the previously reported 2-arylpyridothieno[3,2-<i>d</i>]pyrimidin-4-ones. All the test compounds showed highly potent pim-1 inhibition with IC<sub>50</sub> in the range of 0.06–1.76 µM. No significant difference was detected between the pim-1 inhibitory activity of the 4-pyrimidinone and the 4-imino (=NH) or the cyclised triazolopyrimidine derivatives. The most active compounds were tested for their cytotoxic activity on MCF7 and HCT116 and showed potent activity on both the cell lines.</p>