In this study, a series of novel imperatorin derivatives 7a-7e were designed and synthesized. Their vasorelaxation activities were evaluated by the pharmacological experiments in vitro. Most of the tested compounds exhibited better water solubility and vasorelaxation activity in different degrees, especially 7b and 7c with EC50 values of 2.29 and 2.63 μM, respectively on mesenteric artery, 7d and 7e with EC50 values of 1.04 and 2.65 μM, respectively on brain artery. The results indicated that these novel compounds have a potential interest for the development of novel and potent vasorelaxant agents for different kinds of arteries.