Ashton M J, Ashford A, Loveless A H, Riddell D, Salmon J, Stevenson G V
J Med Chem. 1984 Oct;27(10):1245-53. doi: 10.1021/jm00376a002.
A series of [alpha-(heterocyclyl)benzyl]piperazines was synthesized and their effect of reducing serum cholesterol and triglyceride levels in the rat was evaluated. A systematic exploration of the structure-activity relationships led to the synthesis of (R,S)-(3,5-dimethylisoxazol-4-yl)[4-(1-methylethyl)phenyl] (4-methylpiperazin-1-yl)methane dihydrochloride (M&B 31 426), which had potent activity in lowering serum lipid levels at a daily oral dose of 2 mg/kg and was 100 times more potent than clofibrate.
合成了一系列[α-（杂环基）苄基]哌嗪，并评估了它们对降低大鼠血清胆固醇和甘油三酯水平的作用。通过对构效关系的系统探索，合成了（R，S）-（3,5-二甲基异恶唑-4-基）[4-（1-甲基乙基）苯基]（4-甲基哌嗪-1-基）甲烷二盐酸盐（M&B 31 426），该化合物以每日口服剂量2mg/kg时具有强效的降低血脂水平的活性，且效力比氯贝丁酯强100倍。
