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

Abstract

Reported is the identification of the furo [3,2b]pyridine core as an ovel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway.I nitially, ad iverse 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,a nd highly selective inhibitors of CLKs.P rofiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.

Investigation of Solvent Effect and H-Bonding on Spectroscopic Properties of 1-(3-Amino-6-(2,5-dichlorothiophen-3-yl)-4-phenylfuro[2,3-b]Pyridin-2-yl) Ethenone: Experimental and Computational Study

“…The heterocyclic furo [2,3-b]pyridine moiety is increasingly attracting interest as an important scaffold for many biologically and pharmacologically active compounds. Many of the reported furo [2,3-b]pyridine chemical entities showed unique biological activities as kinase inhibitors and exhibited promising pharmacological activity as anti-cancer and anti-microbial agents [1][2][3][4].…”

Discovery of Potent and Exquisitely Selective Inhibitors of Kinase CK1 with Tunable Isoform Selectivity

“…Since we [15] and others [16] realized that changes of the hinge‐binding motif can have a profound impact on the overall kinase selectivity, we first modified the substituent R5 on the imidazole core using route A in Scheme 1. While the majority of analogs with alternative hinge binders were found to be inactive (Table S1), compound 1 containing the 1 H ‐pyrrolo[2,3‐ b ]pyridine motif exhibited attractive activity (Table 1).…”

An Empirical Quantitative Structure-Activity Relationship Equation Assists the Discovery of High-Affinity Phosphodiesterase 4D Inhibitors as Leads to PET Radioligands

“…22 6-Chloro-2-iodopyridin-3-ol was also synthesized as reported. 52 Other reagents and solvents were purchased from Sigma-Aldrich, AA Blocks, Astatech, and Enamine. Reagents and solvents were used as received unless otherwise stated.…”