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ID: ALA4732242

Journal: Eur J Med Chem

Title: Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core.

Authors: Němec V,Maier L,Berger BT,Chaikuad A,Drápela S,Souček K,Knapp S,Paruch K

Abstract: The furo [3,2-b]pyridine motif represents a relatively underexplored central pharmacophore in the area of kinase inhibitors. Herein, we report flexible synthesis of 3,5-disubstituted furo [3,2-b]pyridines that relies on chemoselective couplings of newly prepared 5-chloro-3-iodofuro [3,2-b]pyridine. This methodology allowed efficient second-generation synthesis of the state-of-the-art chemical biology probe for CLK1/2/4 MU1210, and identification of the highly selective inhibitors of HIPKs MU135 and MU1787 which are presented and characterized in this study, including the X-ray crystal structure of MU135 in HIPK2. chemical biology probe.

CiteXplore: 33636538

DOI: 10.1016/j.ejmech.2021.113299