Diversity-oriented synthesis of angular bis-benzimidazole derivatives under microwave irradiation.
Pharmaceutically interesting, angular bis-benzimidazoles with three appendages have been synthesized successfully through a diversity-oriented approach with soluble support under microwave irradiation. Polymer immobilized o-phenylenediamine was selectively N-acylated with 2-chloro-3-nitrobenzoic acid in a primary aromatic amino moiety. The obtained amide was cyclized to benzimidazole in an acidic condition, and subsequently nucleophilic aromatic substitution with different amines was performed. Successive reduction, cyclization with various aldehydes and activated isothiocyanates yielded angular biheterocyclic benzimidazoles in good quantities. Reaction progress on polymer support was precisely monitored using the conventional proton NMR spectroscopy. Preliminary screening results showed some of these interesting compounds exhibited moderately to good inhibition against vascular endothelial growth factor receptor 3 (VEGFR-3), which is related to invasion and migration of cancer cells.
Chen
Chih-Hau
CH
Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300-10, Taiwan, ROC.
Chien
Ming-Hsien
MH
Kuo
Min-Liang
ML
Chou
Cheng-Ting
CT
Lai
Jin-Ji
JJ
Lin
Shu-Fen
SF
Thummanagoti
Suman
S
Sun
Chung-Ming
CM
D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D008872:Microwaves; D015394:Molecular Structure; D013237:Stereoisomerism
D001562:Benzimidazoles; C031000:benzimidazole