3‐Amino‐1H‐pyrazolopyridine Derivatives as a Maternal Embryonic Leucine Zipper Kinase Inhibitor

Maternal embryonic leucine zipper kinase (MELK) has been implicated in various cellular processes and is highly upregulated in diverse cancers, then it is thought to be a promising anticancer target. 3‐Anilino‐1H‐pyrazolo[3,4‐b]pyridine scaffold was identified as a novel scaffold for MELK kinase inhibitors in high throughput screening (HTS). From exploration for structure–activity relationship (SAR) studies mainly by the modification of the 3 (C3), and 5‐positions (C5), 4‐(4‐methylpiperazin‐1‐yl)‐N‐{5‐[1‐(piperidin‐4‐yl)‐1H‐pyrazol‐4‐yl]‐1H‐pyrazolo[3,4‐b]pyridin‐3‐yl}benzamide (21a) was found to exhibit good activity (IC50 = 0.15 μM) on MELK as a lead in early state.