Design, Synthesis And Bioactivity Studies Of The Novel Ligustrazine Derivatives

Cerebrocardiac Vascular Disease (CVD) seriously threatens peoples' health and more than 45 percent of the death are caused by CVD. Therefore, the research and development of cerebrocardiac vascular drugs are the one of important strategies for the drug therapy in the world.Ligustrazine (Lig., tetramethylpyrazine, TMP) is one major efficient component from Chinese traditional medicine herb Chuanxiong(Ligusticum wallichii Franchat), which is currently widely used in China as a new kind of calcium channel antagonists for the treatment of coronary atherosclerotic cardiovascular disease and ischemic cerebrocardiac vascular disease. Ligustrazine has been reported to inhibit the platelet aggregation, to cause negative chronotropic and inotropic responses on isolated atria, to inhibit vasoconstriction in isolated vascular strips, and to act as a vasodilator, a free radical scavenger, anti-thrombosis and anti-hypertention agent.However, pharmacokinetics studies found that Ligustrazine presented low bioavailability and to be metabolized fast in vivo with short half-life, so accumulated toxicity often appeared in the patients for keeping an effective plasma concentration by the frequent administration. Therefore, it is necessary to develop new generation, high performance and low posion of the cerebrocardiac vascular drugs from molecular modification of Ligustrazine.Studies indicated that pyrazine ring in the molecule of Ligustrazine might largely be the determinant of its phannacodynamics, while the substituted groups...