申请人:E.R. SQUIBB & SONS, INC.
公开号:EP0513761A2
公开(公告)日:1992-11-19
Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthesis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents are provided which have the structure
and analogs thereof, wherein R¹, R², R³ and R⁴ are the same or different and are H, lower alkyl, a metal ion or a prodrug ester;
R⁵ is H, halogen or lower alkyl;
Zq is substituted alkenyl, substituted alkynyl, mixed alkenyl-alkynyl or substituted phenylalkyl, or substituted biphenylalkyl, alkylphenylalkyl or alkyl, including all stereoisomers thereof.
New methods for using such compounds to inhibit cholesterol biosynthesis are also provided.
所提供的化合物是胆固醇生物合成的抑制剂(通过抑制角鲨烯的新生物合成),因此可用作降胆固醇药和抗动脉粥样硬化药,其结构为
及其类似物,其中 R¹、R²、R³ 和 R⁴ 相同或不同,并且是 H、低级烷基、金属离子或原药酯;
R⁵ 是 H、卤素或低级烷基;
Zq 是取代的烯基、取代的炔基、混合烯基-炔基或取代的苯基烷基,或取代的联苯烷基、 烷基苯烷基或烷基,包括其所有立体异构体。
还提供了使用此类化合物抑制胆固醇生物合成的新方法。