[4α,6β(E)]-6-[2-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [4α,6β(E)]-6-[2-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-one
• 英文别名: trans-(+/-)-6-[2-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-one；(4R,6S)-6-[(E)-2-[1-(1,3-benzothiazol-2-yl)-5-(4-fluorophenyl)-3-propan-2-ylpyrazol-4-yl]ethenyl]-4-hydroxyoxan-2-one
• 化学式: C₂₆H₂₄FN₃O₃S
• 分子量: 477.559
• InChiKey: HWIXFBNWTIZBJP-MCBHFWOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-肼基苯并噻唑 在 manganese(IV) oxide 、 sodium hydroxide 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 bis(triphenylphosphine)palladium(II)-chloride 、 三乙基硼 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 、 三甲基乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 42.08h， 生成 [4α,6β(E)]-6-[2-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-one
  参考文献：
  名称：

  Inhibitors of cholesterol biosynthesis. 6. trans-6-[2-(2-N-heteroaryl-3,5-disubstituted-pyrazol-4-yl)ethyl/ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-ones

  摘要：

  A series of N-heteroaryl-substituted mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and in vivo, and to lower plasma cholesterol in a hypercholesterolemic dog model. The goal of the strategy employed was to design an inhibitor which possessed the pharmacological properties of lovastatin (1), and the physicochemical properties (increased hydrophilicity) of pravastatin (2). Two compounds 20a and 20b, were more potent than lovastatin at inhibiting cholesterol biosynthesis both in vitro and in vivo. In terms of plasma cholesterol lowering, 20a was much more efficacious than lovastatin. In addition to possessing increased biological activity, these compounds are significantly less lipophilic than lovastatin, in fact, 20b has a CLOGP value comparable to pravastatin.

  DOI：

  10.1021/jm00089a022

文献信息

• Trans-6-[2-(N-heteroaryl-3,5-disubstituted) pyrazol-4-yl)-ethyl]- or ethenyl] tetrahydro-4-hydroxypyran-2-one-derivatives a process for their preparation and the use thereof
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0252476A2

  公开（公告）日：1988-01-13

  Trans-6-[2-(N -heteroaryl-3,5-disubstituted) pyrazol-4-yl)ethyl]-or ethenyl]tetrahydro-4-hydroxy-2H-pyran-2- one-Derivatives of formula I and the corresponding ring-opened acids derived therefrom which are potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase) and are thus useful hypolipidemic or hypocholesterolemic agents. A process for their manufacture, pharmaceutical compositions containing such compounds, and a method of inhibiting the biosynthesis of cholesterol employing such pharmaceutical compositions are also disclosed.

  反式-6-[2-(N-异芳基-3,5-二取代)吡唑-4-基)乙基]-或乙烯基]四氢-4-羟基-2H-吡喃-2-1-式 I 的衍生物及其衍生的相应开环酸是 3-羟基-3-甲基戊二酰辅酶 A 还原酶（HMG CoA 还原酶）的强效抑制剂，因此是有用的降血脂或降胆固醇药物。 还公开了其制造工艺、含有此类化合物的药物组合物以及使用此类药物组合物抑制胆固醇生物合成的方法。
• US4808621A
  申请人：——

  公开号：US4808621A

  公开（公告）日：1989-02-28