1-Benzyl-3-(5'-hydroxymethyl-2'-furyl)indazole (YC-1) was synthesized in our laboratory as a novel antiplatelet agent initially. We also found that YC-1 had weakly anticancer effect on HL-60 cells in our previous cytotoxicity screening. As part of our continuing search for potential anticancer drug candidates, we have synthesized a series of YC-1 analogues. Initially, methyl 5-(3-methoxybenzoyl)-2-furoate (1) was treated with benzyl- hydrazine to yield a mixture of E- and Z-form isomers (2). Then the hydrazone was treated with lead tetraacetate in dichloromethane at low temperature, subsequently boron trifluoride etherate was added and the mixture was heated to form the expected key intermediate: methyl 5-(1-benzyl-5-methoxy-1H-indazol-3-yl)-2-furoate (4). Finally, starting from compound 4, various esters (8a—8d), amides (9a—9h) and amino acid methyl esters (10a—10f) were synthesized and examined for their cytotoxicity. Among these compounds, 9a showed potential effect on HL-60 cells, 10e showed potential effect on A549 cells, 10f showed the most potential effect on HA22T cells. These finding demonstrated that YC-1 analogues could be developed as novel anticancer agents.
