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 (P-max) of 88.57% at the concentration of 0.1 mmol L-1. Structure-activity relationships of these compounds were discussed. (C) 2003 Elsevier Science Ltd. All rights reserved.