Chem. Pharm. Bull. 53(2) 153—163 (2005)

derivatives (Fig. 1) that showed in vitro and in vivo antitumor activity. These compounds were also found to inhibit tubulin polymerization as a mechanism of their action in cells. To investigate the possibilities for modification of this scaffold, we divided the moieties into five parts from A to E as shown in Fig. 1. So far, it has been reported that the length of the three carbon chain on moiety C and the existence of piperazine on moiety D are important for the activity. In an effort to improve the activity, we replaced the pyrimidine and pyrazole moieties of A and B with some heteroaryl moieties and introduced various substituents to the phenyl ring of moiety E. We describe here the modification of moieties A, B, and E and the antitumor activities of the resulting compounds. Chemistry Syntheses of the 1-arylpyrazolyl compounds (9a—k) were carried out via the route shown in Chart 1. The hydrazine derivatives (5a—j) were subjected to the construction of a pyrazole ring with ethoxymethyleneacetylacetone to provide the 4-acetyl-1-heteroarylpyrazoles (6a—j). Phenylpyrazole derivative (6k) was prepared by following the reported February 2005 Chem. Pharm. Bull. 53(2) 153—163 (2005) 153