Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway PMID: 30569600

ADC Targets in Oncology

2026-04-10

Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway

Angew Chem Int Ed Engl. 2019 Jan 21;58(4):1062-1066. doi: 10.1002/anie.201810312.

Václav Němec ¹ ² , Michaela Hylsová ¹ ² , Lukáš Maier ¹ ² , Jana Flegel ³ , Sonja Sievers ³ , Slava Ziegler ³ , Martin Schröder ⁴ , Benedict-Tilman Berger ⁴ , Apirat Chaikuad ⁴ , Barbora Valčíková ² ⁵ , Stjepan Uldrijan ² ⁵ , Stanislav Drápela ² ⁶ , Karel Souček ² ⁶ , Herbert Waldmann ³ , Stefan Knapp ⁴ , Kamil Paruch ¹ ²

Affiliations

Abstract

Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.

Keywords

biological activity; chemical probes; heterocycles; inhibitors; kinases.