Synthesis of the novel liqustrazine derivatives and Their protective effect on injured vascular endothelial cell damaged by hydrogen peroxide

A series of novel 2-acyloxymethyl-3,5,6-trimethylpyrazine derivatives was designed and synthesized. Most compounds were found to be 1.5–4.5-fold higher potency than tetramethylpyrazine (TMP) in stimulating the proliferation of normal vascular endothelial cells and in protecting against hyperoxic acute injury. The most active one is the 2-nicotinoyl ester 5a exhibiting the maximum proliferation rate (Pmax) of 88.57% at the concentration of 0.1 mmol L−1. Structure–activity relationships of these compounds were discussed.