1-Benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) was has been identified as a potential antitumor agent. In order to extend the structure-activity relationships of YC-1 analogs, in this study a series of selenolo[3,2-c]pyrazoles were synthesized as target compounds.
The key intermediates 7-8 were synthesized by reacting acyl chlorides 5-6 with methyl furan-2-carboxylate. The reacted intermediates 7-8 were then treated with phenylhydrazine or substituted phenylhydrazine to give the corresponding hydrazones 9-17. The above hydrazones were then treated with mixed reagents of lead tetraacetate and boron trifluoride etherate cyclization to yield the designed compounds 27-35. These selenolo[3,2-c]pyrazoles 27-35 were reduced with calcium borohydride to afford their corresponding carbinol derivatives 36-40 and hydrolyzed to give their corresponding carboxylic acids 41-42.The newly synthesized compounds 27-42 were evaluated for their cytotoxicity against human renal A-498 and non-small cell lung cancer NCI-H226 cell lines. The results demonstrate that the carbinol derivatives 3-(5-hydroxymethyl-2-furyl)-1-phenyl-5-methylselenolo[3,2-c]pyrazole- (36) and 3-(5-hydroxymethyl-2-furyl)-1-phenylselenolo[3,2-c]pyrazole-
(37) show significant cytotoxity against human renal cancer cell line A498.
