Novel 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one derivatives as potential anti-cancer agents

A novel series of 3,5,6-trisubstituted pyrazolo[4,3-d]pyrimidin-7-one derivatives, especially 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-ones were synthesized and evaluated for their in vitro anticancer activities against various human cancer cell lines. The inhibitory activities for several kinases have also been tested. The prepared compounds library exhibited significant anticancer activity towards HT-29 colon and DU-145 prostate cancer cell lines. The structure–activity relationships of the 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one scaffold at R1, R2 and R3 have been elucidated. Among the synthesized compounds, 12b was the most active compound with GI50 value of 0.44 μM and 1.07 μM against HT-29 and DU-145 cell lines, respectively, and 13a was the most selective compound towards colon cancer cell line.

Graphical abstractA library of 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one derivatives (I) was synthesized and structure-anticancer activity relationships have been established for R1, R2 and R3. The most active compound 12b showed GI50 value of 0.44 μM and 1.07 μM against cancer cell lines HT-29 and DU-145, respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide