Polymer supported synthesis of novel benzoxazole linked benzimidazoles under microwave conditions: In vitro evaluation of VEGFR-3 kinase inhibition activity
Journal
Organic and Biomolecular Chemistry
Journal Volume
9
Journal Issue
6
Pages
1917-1926
Date Issued
2011
Abstract
An efficient soluble polymer-supported method has been developed for the parallel synthesis of substituted benzimidazole linked benzoxazoles using focused microwave irradiation. The key step involves the amidation of 4-hydroxy-3-nitrobenzoic acid with polymer-immobilized o-phenylenediamine. Application of mild acidic conditions promoted the ring closure to furnish the benzimidazole ring. After hydrogenation of the nitro-group to amine, the resulted polymer conjugates underwent efficient ring closure with various alkyl, aryl and heteroaryl isothiocyanates to generate the polymer-bound benzimidazolyl benzoxazoles. The polymer-bound compounds were finally cleaved from the support to furnish benzimidazole linked benzoxazole derivatives. The efficacy of the resultant angular bis-heterocyclic library was studied against vascular endothelial growth factor receptor (VEGFR-3). The preliminary screening of these novel compounds exhibits moderate to high inhibition (IC 50 = 0.56-1.42 μM). This protocol provides an easy access to novel angular bis-heterocycles which have potential for the discovery of novel leads for targeted cancer therapeutics. ? 2011 The Royal Society of Chemistry.
SDGs
Other Subjects
Amidation; Benzimidazoles; Benzoxazole; Benzoxazole derivatives; Cancer therapeutics; Heterocycles; In-vitro evaluation; Isothiocyanates; Kinase inhibition; Microwave conditions; Mild acidic conditions; Nitrobenzoic acids; O- phenylenediamine; Parallel synthesis; Polymer conjugate; Polymer supported synthesis; Ring closures; Soluble polymers; Vascular endothelial growth factor receptor; Carboxylic acids; Enzyme inhibition; Microwave irradiation; Polymers; benzimidazole derivative; benzoxazole derivative; polymer; protein kinase inhibitor; vasculotropin receptor 3; article; chemical structure; chemistry; drug antagonism; human; IC 50; microwave radiation; synthesis; tumor cell line; Benzimidazoles; Benzoxazoles; Cell Line, Tumor; Humans; Inhibitory Concentration 50; Microwaves; Models, Molecular; Molecular Structure; Polymers; Protein Kinase Inhibitors; Vascular Endothelial Growth Factor Receptor-3
Type
journal article