The discovery of new cytotoxic pyrazolopyridine derivatives

Abstract

A number of new 3,7-disubstituted pyrazolo[3,4-c]pyridines have been designed and synthesized from suitable 2-aminopyridines. The antiproliferative activity of the derivatives was determined against the pancreatic MIA PaCa-2 and ovarian SCOV3 cancer cell-lines. IC₅₀ values of the most promising analogue 46 lie in the submicromolar or low micromolar range. Furthermore, compound 46 shows similar inhibitory activities against DU145, A2058 and PC-3 cancer cells, blocks the cell cycle at the G₀/G₁ phase and induce apoptosis, as determined by the appearance of apoptotic nuclei.

Keywords: Antiproliferative activity; Cell-cycle selectivity; Deazapurines; Pyrazolo[3,4-c]pyridine; Suzuki coupling.