Synthesis of some substituted furo[3,2-g]chromeno[2,3-c]pyrazole and pyrazoline derivatives from 5-hydroxybergapten and 5-hydroxyisopimpinellin as EGFR and VEGFR-2 kinase inhibitors

Abstract

A series of substituted 7H-furo[3,2-g]chromen-7-one and furo[3,2-g]chromeno[2,3-c]pyrazole derivatives (2–9) were synthesized by using 5-hydroxy-4-methoxy-7H-furo[3,2-g]chromen-7-one (5-hydroxybergapten) and 5-hydroxy-4,9-dimethoxy-7H-furo[3,2-g]chromen-7-one (5-hydroxyisopimpinellin) (1) as starting materials. Compound 1 reacted with amino acid esters to give the corresponding 5-N-amino acid derivatives 2 and 3, respectively. Bromination of 1 gave the corresponding 6-bromo analouges 4, that were treated with amino acids esters to give the corresponding 6-N-amino acids analogues 5. Treatment of the later with hydrazine hydrate led to cleavage of the pyran ring and gave the corresponding pyrazoline benzofuran derivatives 6. Formylation of 1 gave aldehyde derivative 7, which was condensed with amino acid to give the corresponding 5-N-amino-6-formyl derivatives 8. Cyclization of compounds 8 with hydrazine hydrate gave the corresponding pyrazoline derivatives 9. All synthesized compounds were tested as EGFR and VEGFR-2 kinase inhibitors.