he hypothesis of piperidone inhibitors of farnesyltransferase was built with the computer-aided drug design software—Catalyst. According to the hypothesis and structure-activity relationship of piperidone inhibitors, 17 novel piperidone inhibitors of farnesyltransferase were designed and synthesized. All compounds were characterized by IR, MS and ¹H NMR. The IC₅₀ value of the target compounds against human Hela cells was evaluated and the result showed that all compounds exhibited antitumor activity, furthermore, the IC₅₀ value of eleven compounds was smaller than that of 5-Fu. The tested activities of the target compounds were fit to those estimated using the hypothesis that was built by Catalyst, and the excellent correlation was got.

Key words: piperidone inhibitor of farnesyltransferase, computer-aided drug design, hypothesis, structure-activity relationship, antitumor activity