申请人:Meiji Seika Kaisha, Ltd.
公开号:US06417362B1
公开(公告)日:2002-07-09
Disclosed are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof. The compounds can inhibit the biosynthesis of triglycerides in the liver and can inhibit the secretion of lipoprotein containing apolipoprotein B from the liver. Therefore, they are useful for the prevention or treatment of hyperlipidemia (particularly hyper-very-low-density-lipoproteinemia) and arteriosclerotic diseases, such as cardiac infarction, or pancreatitis induced by hyperlipidemia.
wherein A represents group —CR1R2—(CH2)i— where R1 and R2 each represent a hydrogen atom or alkyl, —CH═CH—, —O—CH2—, or —S(O)j—CH2—; B represents a hydrogen or halogen atom; X represents —CR3R4R5, —NR6R7, —(CH2—CH═C(CH3)—CH2)p—CH2CH═C(CH3)2, alkyl, cycloalkyl, phenyl, cinnamyl, or heteroaromatic ring; Y represents —(CH2)q—, —CH═CH—, —NR8—, an oxygen atom, or a bond; Z represents carbonyl or a bond; K represents alkylene or a bond; L represents —CH═CH— or a bond; and M represents a hydrogen atom, alkyl, cycloalkyl, phenyl, heterocyclic ring, biphenyl, or diphenylmethyl.
本发明涉及由公式(I)表示的化合物及其药学上可接受的盐和溶剂化物。这些化合物可以抑制肝脏中三酰甘油的生物合成,并可以抑制含载载脂蛋白B的脂蛋白从肝脏分泌。因此,它们对于预防或治疗高脂血症(特别是高超低密度脂蛋白血症)和动脉硬化性疾病,如心肌梗死或由高脂血症引起的胰腺炎是有用的。其中A代表基团—CR1R2—(CH2)i—,其中R1和R2分别代表氢原子或烷基,—CH═CH—,—O—CH2—或—S(O)j—CH2—;B代表氢或卤原子;X代表—CR3R4R5,—NR6R7,(CH2—CH═C(CH3)—CH2)p—CH2CH═C(CH3)2,烷基,环烷基,苯基,肉桂基或杂环芳香环;Y代表—(CH2)q—,—CH═CH—,—NR8—,氧原子或键;Z代表羰基或键;K代表烷基或键;L代表—CH═CH—或键;M代表氢原子,烷基,环烷基,苯环,杂环环,联苯或二苯甲基。