3-Amino-1 H-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-1 H-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)-1 H-pyrazol-4-yl]-1 H-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. [ABSTRACT FROM AUTHOR]