N-heptyl-5-hydroxypentanamide | 130804-27-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-heptyl-5-hydroxypentanamide
• 英文别名: Pentanamide, N-heptyl-5-hydroxy-
• CAS: 130804-27-2
• 化学式: C₁₂H₂₅NO₂
• 分子量: 215.336
• InChiKey: GEEOSOJYLJGOKG-UHFFFAOYSA-N

物化性质

• 熔点：
  54-55 °C
• 沸点：
  384.8±25.0 °C(Predicted)
• 密度：
  0.935±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-heptyl-5-hydroxypentanamide 在 lithium aluminium tetrahydride 、 四溴化碳 、 sodium hydride 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 来西贝特
  参考文献：
  名称：

  酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂：一系列新的三取代咪唑的合成及结构活性关系研究。

  摘要：

  已经合成了一系列的4,5-二芳基-2-（取代硫代）-1H-咪唑，并被证明是酰基辅酶A：胆固醇酰基转移酶（ACAT）的有效抑制剂。本文报道了该系列的设计，合成和结构活性关系。该系列的化合物之一，N'-（2,4-二氟苯基）-N- [5-[（4,5-二芳基-1H-咪唑-2-基）硫代]戊基] -N-庚基脲（DuP 128）被选作肠道活性ACAT抑制剂进行开发。DuP 128是一种有效的体外和体内ACAT抑制剂，可抑制大鼠肝微粒体中的ACAT，IC50 = 10 nM，并且在体内具有有效的抗高胆固醇血症活性。

  DOI：

  10.1021/jm00047a009
• 作为产物：
  描述：

  delta-戊内酯 、 庚胺 以 甲苯 为溶剂， 生成 N-heptyl-5-hydroxypentanamide
  参考文献：
  名称：

  哒嗪衍生物作为新型酰基-Coa：胆固醇酰基转移酶（ACAT）抑制剂

  摘要：

  酰基辅酶A：胆固醇酰基转移酶（EC2.3.1.26，ACAT）是一种微粒体酶，可通过将胆固醇与长链脂肪酰基辅酶A酰化来催化胆固醇酯的形成[1]。

  DOI：

  10.1002/jhet.5570420306

文献信息

• Use of imidazoles for the treatment of atherosclerosis
  申请人：Du Pont Merck Pharmaceutical Company

  公开号：US05166214A1

  公开（公告）日：1992-11-24

  This invention relates to imidazoles as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT), processes for their preparation, and their use as antihypercholesterolemic agents or antiatherosclerotic. The compounds for use in the described method are compounds of Formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are selected independently from H, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, C.sub.7 -C.sub.14 araalkyl, phenyl optionally substituted with 1 to 3 groups selected from F, Cl, Br, OH, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.8 branched alkyl, CH.sub.3 S(O).sub.r, NO.sub.2, CF.sub.3, or NR.sup.7 R.sup.8 ; R.sup.3 is H, C.sub.1 -C.sub.6 alkyl, allyl, benzyl, or phenyl optionally substituted with F, Cl, CH.sub.3, CH.sub.3 O, or CF.sub.3 ; R.sup.4 is straight chain C.sub.1 -C.sub.8 alkyl optionally substituted with F; C.sub.3 -C.sub.8 branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, C.sub.7 -C.sub.14 aralkyl where the aryl group is optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8, or NCOR.sup.7 ; C.sub.3 -C.sub.6 alkenyl or alkynyl, C.sub.1 -C.sub.3 perfluoroalkyl, phenyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.8 branched alkyl, C.sub.1 -C.sub.4, alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8 or NCOR.sup.7 ; pentafluorophenyl, benzyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8, or NCOR.sup.7 ; 2-, 3-, or 4- or pyrindinyl, pyrimidinyl, or biphenyl; R.sup.5 is H, C.sub.1 -C.sub.6 alkyl, or benzyl; R.sup.6 is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.8 alkenyl of alkynyl, phenyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8, or NCOR.sup.7 ; pentafluorophenyl, benzyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8, or NCOR.sup.7 ; R.sup.7 and R.sup.8 are selected independently from H or C.sub.1 -C.sub.4 alkyl; A is C.sub.2 -C.sub.10 alkyl, C.sub.3 -C.sub.10 branched alkyl, C.sub.3 -C.sub.10 alkenyl, or C.sub.3 -C.sub.10 alkynyl; Y is O; Z is NHR.sup.4, OR.sup.4, or R.sup.4 ; r is 0-2, or a pharmaceutically acceptable salt thereof.

  这项发明涉及咪唑作为酰基辅酶A：胆固醇酰基转移酶（ACAT）的抑制剂，其制备方法以及它们作为抗高胆固醇药物或抗动脉粥样硬化药物的用途。所述方法中用于的化合物为式（I）的化合物：##STR1## 其中R.sup.1和R.sup.2分别选择自H，C.sub.1 -C.sub.8烷基，C.sub.3 -C.sub.8支链烷基，C.sub.3 -C.sub.7环烷基，C.sub.4 -C.sub.10环烷基烷基，C.sub.7 -C.sub.14芳基烷基，苯基，可选择地取代为1至3个来自F，Cl，Br，OH，C.sub.1 -C.sub.4烷氧基，C.sub.1 -C.sub.4烷基，C.sub.3 -C.sub.8支链烷基，CH.sub.3S（O）.sub.r，NO.sub.2，CF.sub.3或NR.sup.7R.sup.8的基团；R.sup.3为H，C.sub.1 -C.sub.6烷基，烯丙基，苄基，或可选择地取代为F，Cl，CH.sub.3，CH.sub.3O或CF.sub.3的苯基；R.sup.4为直链C.sub.1 -C.sub.8烷基，可选择地取代为F；C.sub.3 -C.sub.8支链烷基，C.sub.3 -C.sub.7环烷基，C.sub.4 -C.sub.10环烷基烷基，C.sub.7 -C.sub.14芳基烷基，其中芳基可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基或烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8，或NCOR.sup.7；C.sub.3 -C.sub.6烯基或炔基，C.sub.1 -C.sub.3全氟烷基，苯基，可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基，C.sub.3 -C.sub.8支链烷基，C.sub.1 -C.sub.4烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8或NCOR.sup.7；五氟苯基，苄基，可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基或烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8，或NCOR.sup.7；2-，3-，或4-或吡啶基，嘧啶基，或联苯基；R.sup.5为H，C.sub.1 -C.sub.6烷基，或苄基；R.sup.6为C.sub.1 -C.sub.8烷基，C.sub.3 -C.sub.8支链烷基，C.sub.3 -C.sub.7环烷基，C.sub.3 -C.sub.8烯基或炔基，苯基，可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基或烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8，或NCOR.sup.7；五氟苯基，苄基，可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基或烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8，或NCOR.sup.7；R.sup.7和R.sup.8分别选择自H或C.sub.1 -C.sub.4烷基；A为C.sub.2 -C.sub.10烷基，C.sub.3 -C.sub.10支链烷基，C.sub.3 -C.sub.10烯基，或C.sub.3 -C.sub.10炔基；Y为O；Z为NHR.sup.4，OR.sup.4，或R.sup.4；r为0-2，或其药用盐。
• Design, Synthesis, and Structure-Activity Relationship Studies for a New Imidazole Series of J774 Macrophage Specific Acyl-CoA:Cholesterol Acyltransferase (ACAT) Inhibitors
  作者：Thomas P. Maduskuie、Richard G. Wilde、Jeffrey T. Billheimer、Debra A. Cromley、Sandra Germain、Peter J. Gillies、C. Anne Higley、Alex L. Johnson、Penio Pennev、Edward J. Shimshick、Ruth R. Wexler

  DOI：10.1021/jm00007a004

  日期：1995.3

  Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification. Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the development of fatty streaks. Inhibitors of the ACAT enzyme may retard this atherogenic process

  酰基辅酶A：胆固醇酰基转移酶（ACAT）是参与细胞内胆固醇酯化的主要酶。巨噬细胞的动脉壁浸润和随后的胆固醇不受控制的酯化导致泡沫细胞形成被认为是导致脂肪条纹发展的重要过程。ACAT酶的抑制剂可能会延迟该动脉粥样硬化过程。我们最近发现了一系列咪唑，它们在J774巨噬细胞细胞培养测定中是有效的体外ACAT抑制剂。本文将描述这一系列非常有效的化合物的设计，合成和结构-活性关系。
• Benzimidazoles for the treatment of atherosclerosis
  申请人：The Du Pont Merck Pharmaceutical Company

  公开号：US05290801A1

  公开（公告）日：1994-03-01

  This invention relates to imidazoles, namely, fused-ring heterocycles as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT), pharmaceutical compositions containing them, processes for their preparation, and their use as antihypercholesterolemic and/or antiatherosclerotic agents for the treatment of atherosclerosis.

  这项发明涉及咪唑类化合物，即融合环杂环化合物，作为酰基辅酶A：胆固醇酰基转移酶（ACAT）的抑制剂，包含它们的药物组合物，它们的制备方法，以及它们作为抗高胆固醇和/或抗动脉粥样硬化药物用于治疗动脉粥样硬化。
• Sulfonate ester
  申请人：Eastman Kodak Company

  公开号：US05220041A1

  公开（公告）日：1993-06-15

  Omega-alkanesulfonoxyalkanamides which are useful as alkylating agents are provided. Such alkylating agents are particularly useful for appending groups of the formula --Y--CONR.sup.8 R.sup.9 wherein Y is selected from the group consisting of unsubstituted or substituted trimethylene, tetramethylene, or pentamethylene; and R.sup.8 and R.sup.9 are hydrogen or various hydrocarbyl radicals onto electrophilic sulfur, oxygen or nitrogen moieties.

  提供了作为烷基化剂有用的Omega-烷基磺酸氧烷酰胺。这样的烷基化剂对于将式中的基团附加到亲电性硫、氧或氮官能团上特别有用，其中Y选择自未取代或取代的三亚甲基，四亚甲基或五亚甲基；而R8和R9是氢或各种碳氢基团。
• Preparation of omega-substituted alkanamide
  申请人：Eastman Kodak Company

  公开号：US05212318A1

  公开（公告）日：1993-05-18

  A method for the preparation of omega-arylthioalkanamides, especially omega-imidazolylthioalkanamides useful, for example, in the preparation of certain antihypercholesterolemic agents is disclosed. The method involves three steps including an addition reaction between a lactone and an amine to produce an omega-hydroxyalkanamide; a condensation reaction between said omega-hydroxyalkanamide and an alkanesulfonic acid halide or anhydride to produce an alkanesulfonate ester; reaction of said alkanesulfonate ester with a salt of an aromatic mercaptan, especially an imidazole-2-thiol, to produce the omega-imidazolylthioalkanamides.

  本发明公开了一种制备ω-芳基硫代烷酰胺的方法，特别是制备某些抗高胆固醇药物中有用的ω-咪唑基硫代烷酰胺。该方法包括三个步骤，包括一种内酯和胺之间的加成反应，以产生ω-羟基烷酰胺；一种ω-羟基烷酰胺与烷基磺酸卤或酸酐的缩合反应，以产生烷基磺酸酯；将所述烷基磺酸酯与芳香硫醇的盐，特别是咪唑-2-硫醇反应，以产生ω-咪唑基硫代烷酰胺。