title: Polymer supported synthesis of novel benzoxazole linked benzimidazoles under microwave conditions: in vitro evaluation of VEGFR-3 kinase inhibition activity.
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.
authors.affiliation: Department of Applied Chemistry, National Chiao Tung University, Hsinchu, 300-10, Taiwan.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Chanda
authors.forename: Barnali
authors.initials: B
authors.lastname: Maiti
authors.forename: Gorakh S
authors.initials: GS
authors.lastname: Yellol
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Sun
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry*; D001583:Benzoxazoles / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008872:Microwaves; D008958:Models, Molecular; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000037:antagonists & inhibitors*
chemical_list: D001562:Benzimidazoles; D001583:Benzoxazoles; D011108:Polymers; D047428:Protein Kinase Inhibitors; D040321:Vascular Endothelial Growth Factor Receptor-3