Polymer supported synthesis of novel benzoxazole linked benzimidazoles under microwave conditions: in vitro evaluation of VEGFR-3 kinase inhibition activity |
| |
Authors: | Chanda Kaushik Maiti Barnali Yellol Gorakh S Chien Ming-Hsien Kuo Min-Liang Sun Chung-Ming |
| |
Institution: | Department of Applied Chemistry, National Chiao Tung University, Hsinchu, 300-10, Taiwan. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|