Chem. Pharm. Bull. 55(6) 922—925 (2007)

as an anti-angiogenesis agent by Ladouceur et al. These compounds have a potent inhibitory effect on the growth of tumor cells with angiogenesis activity. We have also carried out a structure–activity relationship (SAR) study of 3-(indol2-yl)quinoxalin-2-ones, which showed a potent inhibitory activity toward the VEGF-induced proliferation of human mesangial cells and the VEGF-induced auto-phosphorylation of human umbilical vein endothelial cells. Moreover, these compounds have a potent medicinal effect based on anti-angiogenic action, by oral administration (Chart 1, 9). On the other hand, as shown in Chart 2, the two conventional synthetic method of 3-(indol-2-yl)quinoxalin-2-ones VI had been also reported. One of them is the A-route consisting of the crossing coupling of (indol-2-yl)boric acids with 2,3-dichloroquinoxalines. Another is the B-route in which (indol-2-yl)oxoacetate is condensed with phenylenediamine. In the case of the former, II was prepared by the reaction of I, which was protected at the 1-position of indole with a suitable protecting group, with a boric acid ester using an alkyl lithium reagent. Then III was prepared by the crossing coupling of II with 2,3-dichloroquinoxalines, which had previously been prepared separately. This route requires strict anhydrous conditions and low temperature. Moreover, two kinds of regioisomers of III might be generated by the coupling reaction of II with the substituted 2,3-dichloroquinoxalines. On the other hand, in the case of the latter route, the preparation of IV also needs strict anhydrous conditions and low temperature like A-route. In addition, V may be obtained as two different regioisomers by the reaction of IV with the substituted phenylenediamines. When more complicated derivatives are prepared for more extensive SAR studies, it could be expected that the number of steps would increase 922 Vol. 55, No. 6