N'-{2,4-difluorophenyl)-N-heptyl-N-5-hydroxypentylurea | 139772-88-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N'-{2,4-difluorophenyl)-N-heptyl-N-5-hydroxypentylurea
• 英文别名: N-(2,4-difluorophenyl)-N'-heptyl-N'-(5-hydroxypentyl)urea；N'-(2,4-difluorophenyl)-N-heptyl-N-(5-hydroxypentyl)urea；N'-(2,4-difluorophenyl)-N-heptyl-N-5-hydroxypentylurea；Urea, N'-(2,4-difluorophenyl)-N-heptyl-N-(5-hydroxypentyl)-；3-(2,4-difluorophenyl)-1-heptyl-1-(5-hydroxypentyl)urea
• CAS: 139772-88-6
• 化学式: C₁₉H₃₀F₂N₂O₂
• 分子量: 356.456
• InChiKey: YFZFEANXQSVQGV-UHFFFAOYSA-N

物化性质

• 沸点：
  494.4±45.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N'-{2,4-difluorophenyl)-N-heptyl-N-5-hydroxypentylurea 在 四溴化碳 、 sodium hydride 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 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 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 N'-{2,4-difluorophenyl)-N-heptyl-N-5-hydroxypentylurea
  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。
• Fused-ring heterocycles for the treatment of atherosclerosis
  申请人：The Du Pont Merck Pharmaceutical Company

  公开号：US05478830A1

  公开（公告）日：1995-12-26

  This invention relates to pyrazolo pyrimidines for the treatment of atherosclerosis as inhibitors of acyl--CoA, cholesterol acyetransferase (ACAT), and their use as antihypercholesterolemic agents, pharmaceutical compositions and preparation, and having the formula (I): ##STR1## wherein: A and Q are selected independently from CH or N with no more than two nitrogens per ring: D, E, and G are selected independently from CR.sup.1 or N with no more than two nitrogens per ring; X is S(O).sub.r, O, NR.sup.4 or CH.sup.2 ; J 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, S, H.sub.2 or NH: Z is NHR.sup.3, OR.sup.3 or R.sup.3 : R.sup.1 is selected independently from H, NO.sub.2, Br, Cl, F, CF.sub.3, CN, CH.sub.3 S(O).sub.r, C.sub.1 -C.sub.8 alkyl or alloxy, C.sub.3 -C.sub.8, branched alkyl, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.5 R.sup.6 or NR.sup.5 COR.sup.6 ; R.sup.2 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 or alkynyl, C.sub.7 -C.sub.14 araalkyl where the aryl group is optionally substituted; phenyl optionally substituted benzyl optionally substituted 2-, 3-, or 4- pyridinyl, pyrimidinyl: or biphenyl: R.sup.3 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.4 -C.sub.10 cycloallylalkyl, C.sub.3 -C.sub.6 alkenyl or alkynyl, C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.7 -C.sub.14 araalkyl where the aryl group is optionally substituted phenyl optionally substituted benzyl optionally substituted 2-, 3-, or 4- pyridinyl, pyrimidinyl; or biphenyl: R.sup.4 is H, C.sub.1 -C.sub.6 alkyl or benzyl; R.sup.5 and R.sup.6 are selected independently from H or C.sub.1 -C.sub.4 alkyl; r is 0 to 2: or a pharmaceutically acceptable salt thereof.

  本发明涉及用于治疗动脉硬化的吡唑嘧啶类化合物，作为酰基-CoA胆固醇酰基转移酶（ACAT）的抑制剂以及其作为降低胆固醇的药物剂量形式和制备方法，其化学式为（I）：##STR1##其中：A和Q独立选择自CH或N，每个环中不超过两个氮原子；D、E和G独立选择自CR.sup.1或N，每个环中不超过两个氮原子；X是S（O）.sub.r，O，NR.sup.4或CH.sup.2；J是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是O，S，H.sub.2或NH；Z是NHR.sup.3，OR.sup.3或R.sup.3；R.sup.1独立选择自H，NO.sub.2，Br，Cl，F，CF.sub.3，CN，CH.sub.3S（O）.sub.r，C.sub.1-C.sub.8烷基或异氧基，C.sub.3-C.sub.8，支链烷基，C.sub.1-C.sub.4羧基烷氧基，NR.sup.5R.sup.6或NR.sup.5COR.sup.6；R.sup.2是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，C.sub.7-C.sub.14芳基烷基，其中芳基基团可选地被取代；苯基可选地被取代的苄基，2-，3-或4-吡啶基，嘧啶基；或联苯基；R.sup.3是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环丙烷基，C.sub.3-C.sub.6烯基或炔基，C.sub.1-C.sub.3全氟烷基，C.sub.7-C.sub.14芳基烷基，其中芳基基团可选地被取代，苯基可选地被取代的苄基，2-，3-或4-吡啶基，嘧啶基；或联苯基；R.sup.4是H，C.sub.1-C.sub.6烷基或苄基；R.sup.5和R.sup.6独立选择自H或C.sub.1-C.sub.4烷基；r为0至2；或其药学上可接受的盐。
• Imidazoles for the treatment of atherosclerosis
  申请人：The Du Pont Merck Pharmaceutical Company

  公开号：US05318984A1

  公开（公告）日：1994-06-07

  Disclosed are compounds of the formula ##STR1## wherein R.sup.1 and R.sup.2 are selected independently from H, C.sub.1 -C.sub.8 unbranched 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, 2-, 3- or 4-pyridinyl, 2-thienyl, 2-furanyl, 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 ; or ##STR2## where L is O, O(CH.sub.2).sub.m+1 O, or (CH.sub.2).sub.m where m is 0-4; 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 araalkyl 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, 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 or 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; X is S(O).sub.r, O, NR.sup.5, CH.sub.2 ; 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, S, H.sub.2, or NH; Z is NHR.sup.4, OR.sup.4, or R.sup.4 ; r is 0-2, or a pharmaceutically acceptable salt thereof and their use as antihypercholesterolemic agents or antiatherosclerotic agents.

  本发明涉及的化合物的结构式为：##STR1##其中R.sup.1和R.sup.2独立选择自H，C.sub.1-C.sub.8直链烷基，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 araalkyl，2-、3-或4-吡啶基，2-噻吩基，2-呋喃基，苯基，其可选地被1至3个选自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的基取代；或##STR2##其中L为O、O(CH.sub.2).sub.m+1O或(CH.sub.2).sub.m，其中m为0-4；R.sup.3为H、C.sub.1-C.sub.6烷基、烯丙基、苄基或其可选地被F、Cl、CH.sub.3、CH.sub.3O或CF.sub.3取代的苯基；R.sup.4为直链C.sub.1-C.sub.8烷基，其可选地被F取代；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 araalkyl，其中芳基基团可选地被1至3个选自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的基取代；C.sub.3-C.sub.6烯基或炔基，C.sub.1-C.sub.3全氟烷基，其可选地被1至3个选自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的基取代的苯基；五氟苯基，其可选地被1至3个选自C.sub.1-C.sub.4烷基或烷氧基、F、Br、Cl、NH.sub.2、OH、CN、CO.sub.2H、嘧啶基或联苯基的基取代的苄基；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，其可选地被1至3个选自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的基取代的苯基；五氟苯基，其可选地被1至3个选自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的基取代的苄基；R.sup.7和R.sup.8独立选择自H或C.sub.1-C.sub.4烷基；X为S(O).sub.r、O、NR.sup.5、CH.sub.2；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、S、H.sub.2或NH；Z为NHR.sup.4、OR.sup.4或R.sup.4；r为0-2或其药学上可接受的盐，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。