Scaffold oriented synthesis. Part 4: Design, synthesis and biological evaluation of novel 5-substituted indazoles as potent and selective kinase inhibitors employing heterocycle forming and multicomponent reactions

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 5; pp. 1480 - 1483
• Main Authors: Akritopoulou-Zanze, Irini, Wakefield, Brian D., Gasiecki, Alan, Kalvin, Douglas, Johnson, Eric F., Kovar, Peter, Djuric, Stevan W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-03-2011; Elsevier
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; chemical derivatives; chemical reactions; Drug Design; Egfr inhibitors; enzyme inhibitors; Enzymes and enzyme inhibitors; epidermal growth factor receptors; Fundamental and applied biological sciences. Psychology; Gsk3β inhibitors; heterocyclic compounds; Heterocyclic Compounds - chemistry; Imidazopyridines; Imidazopyrimidine; Indazoles - chemical synthesis; Indazoles - chemistry; Indazoles - pharmacology; Kinase inhibitors; Kinase scaffolds; MCR; Medical sciences; Miscellaneous; Molecular Structure; multicomponent reactions; Pharmacology. Drug treatments; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; protein-serine-threonine kinases; Rock2 inhibitors; Structure-Activity Relationship; synthesis; Transferases; Van Leusen reactions; Kinase scaffolds; Imidazopyridines; Egfr inhibitors; Imidazopyrimidine; Rock2 inhibitors; Kinase inhibitors; Gsk3β inhibitors; MCR; Van Leusen reactions; Imidazole derivatives; Five membered ring; Angular nitrogen heterocycle; Nitrogen heterocycle; Thiazole derivatives; Non-specific serine/threonine protein kinase; Selectivity; Epidermal growth factor receptor; Signal transduction; Imidazopyridine derivatives; Structure activity relation; Bicyclic compound; Imidazothiazole derivatives; Receptor protein-tyrosine kinase; Aromatic compound; Chemical synthesis; Tau-protein kinase; Sulfur nitrogen heterocycle; multicomponent reactions; Multicomponent reaction; Enzyme; Transferases; Enzyme inhibitor; Indazole derivatives; In vitro
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.01.001

We report the synthesis and biological evaluation of 5-substituted indazoles as kinase inhibitors. The compounds were synthesized in a parallel synthesis fashion from readily available starting materials employing heterocycle forming and multicomponent reactions and were evaluated against a panel of kinase assays. Potent inhibitors were identified for Gsk3β, Rock2, and Egfr.
We report the synthesis and biological evaluation of 5-substituted indazoles as kinase inhibitors. The compounds were synthesized in a parallel synthesis fashion from readily available starting materials employing heterocycle forming and multicomponent reactions and were evaluated against a panel of kinase assays. Potent inhibitors were identified for Gsk3β, Rock2, and Egfr.