Ligustrazine Derivatives. Part 8: Design, Synthesis, and Preliminary Biological Evaluation of Novel Ligustrazinyl Amides as Cardiovascular Agents

A series of novel Ligustrazinyl amides was designed, synthesized and evaluated for their protective effect on the injured vascular endothelial cells. The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured human umbilical vascular endothelial cells (HUVECs) that is damaged by hydrogen peroxide. Among the active compounds, compounds 8i, 8t and 8u exhibited the highest potency with low EC50 values of 0.037, 0.070 and 0.055 mM, respectively. Structure-activity relationships were briefly discussed. Keywords: Ligustrazine, pyrazine amides, synthesis, cardiovascular disease.