6-(2-Morpholinoethyl)-thiazolo[3,2-a]pyrimidin-5-one: A novel scaffold for the synthesis of potential PI3kα inhibitors

The present study involves the development of certain thiazolo[3,2-a]pyrimidin-5-ones linked through an ethylene bridge to various amines. The newly synthesized compounds 4-6(a-c) were subjected to in vitro anticancer evaluation using NCI antitumor screening. The target compounds showed observed activity against Renal UO-31 cancer cell line with cell growth promotion 52.72-64.52%. COMPARE analyses revealed compounds 4a and 4b exhibiting high correlation levels with rapamycin (mTOR inhibitor). Kinase assays were performed for compounds 4a and 4b on mTOR and structurally-related PI3Kα. They displayed moderate activity against PI3Kα with IC50 values of 120 and 151 μM, respectively. Compounds 4a and 4b could thus be considered as a promising leading scaffold for further development of potential PI3Kα inhibitors.