A series of 1-(3-dimethylaminopropyl)indolin-2-one derivatives were designed and synthesized based on the structural features of TMP-20, LK-B030, and BX-517. These newly synthesized derivatives were evaluated for in vitro activity against five human cancer cell lines and three HUVECs. Results revealed that all of the target compounds 1a–h generally show potent activity against these cancer cell lines and higher selectivity on VEGF- and bFGFstimulated HUVECs than HUVEC. In particular, 1f (IC50s: 1.10–1.47 lM) is 1.8–6.0-fold more potent than sunitinib against MDA-MB-231, A549, HL-60 and K-562, and 1.6–2.8-fold more potent than LK-B030 against MDA-MB-231 and A549.