4,5-diphenyl-1-<<2-(trimethylsilyl)ethoxy>methyl>-1H-imidazole | 139772-93-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4,5-diphenyl-1-<<2-(trimethylsilyl)ethoxy>methyl>-1H-imidazole
• 英文别名: 4,5-diphenyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole；4,5-diphenyl-1-[(trimethylsilyl)ethoxymethyl]-1H-imidazole；2-[(4,5-diphenylimidazol-1-yl)methoxy]ethyl-trimethylsilane
• CAS: 139772-93-3
• 化学式: C₂₁H₂₆N₂OSi
• 分子量: 350.536
• InChiKey: YMLXEAHHDZVWRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.53
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,5-diphenyl-1-<<2-(trimethylsilyl)ethoxy>methyl>-1H-imidazole 在 potassium fluoride 、 potassium phosphate 、 copper(l) iodide 、 四(三苯基膦)钯 、 正丁基锂 、 1,1'-bis(diisopropylphosphino)ferrocene 、 三乙胺 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 potassium thioacetate 作用下， 以 四氢呋喃 、 正己烷 、 丙酮 、 甲苯 为溶剂， 反应 0.5h， 生成 2-(6-(4,5-diphenyl-1-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-imidazol-2-yl)dithieno[3,2-b:2',3'-d]thiophen-2-yl)-4,5-diphenyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole
  参考文献：
  名称：

  杂环成环对奎宁硫并苯衍生物中近红外吸光度的影响。

  摘要：

  描述了一系列醌类含硫咪唑基取代杂并苯的同系物的合成和表征。通过紫外/可见光、荧光和 EPR 光谱以及量子化学计算研究了其光电和磁性能，并与相应的苯并同系物进行了比较。室温和大气稳定的醌型化合物在 678 至 819 nm 之间的近红外区域显示出强吸收。二噻吩并[3,2-b:2',3'-d]噻吩和噻吩并[2',3':4,5]噻吩并[3,2-b]噻吩并[2,3-d]噻吩衍生物EPR 在室温下具有活性。对于后者，变温 EPR 光谱揭示了热可接近三重态的存在，单重态-三重态分离为 14.1 kJ mol-1 。

  DOI：

  10.1002/chem.202200478
• 作为产物：
  描述：

  4,5-二苯基咪唑 、 2-(三甲基硅烷基)乙氧甲基氯 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 以93 %的产率得到4,5-diphenyl-1-<<2-(trimethylsilyl)ethoxy>methyl>-1H-imidazole
  参考文献：
  名称：

  杂环成环对奎宁硫并苯衍生物中近红外吸光度的影响。

  摘要：

  描述了一系列醌类含硫咪唑基取代杂并苯的同系物的合成和表征。通过紫外/可见光、荧光和 EPR 光谱以及量子化学计算研究了其光电和磁性能，并与相应的苯并同系物进行了比较。室温和大气稳定的醌型化合物在 678 至 819 nm 之间的近红外区域显示出强吸收。二噻吩并[3,2-b:2',3'-d]噻吩和噻吩并[2',3':4,5]噻吩并[3,2-b]噻吩并[2,3-d]噻吩衍生物EPR 在室温下具有活性。对于后者，变温 EPR 光谱揭示了热可接近三重态的存在，单重态-三重态分离为 14.1 kJ mol-1 。

  DOI：

  10.1002/chem.202200478

文献信息

• Acyl CoA:Cholesterol Acyltransferase (ACAT) Inhibitors: Synthesis and Structure-Activity Relationship Studies of a New Series of Trisubstituted Imidazoles
  作者：C. Anne Higley、Richard G. Wilde、Thomas P. Maduskuie、Alexander L. Johnson、Pennio Pennev、Jeffrey T. Billheimer、Candy S. Robinson、Peter J. Gillies、Ruth R. Wexler

  DOI：10.1021/jm00047a009

  日期：1994.10

  to be potent inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). The design, synthesis, and structure-activity relationships for this series are reported herein. One of the compounds from this series, N'-(2,4-difluorophenyl)-N-[5-[(4,5-diaryl-1H-imidazol-2- yl)thio]pentyl]-N-heptylurea (DuP 128), was selected for development as an intestinally active ACAT inhibitor. DuP 128 is a potent ACAT inhibitor

  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。
• 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.

  本发明涉及咪唑类化合物作为酰基辅酶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和抗动脉粥样硬化剂的用途。所述方法中使用的化合物为式（I）的化合物：其中R.sup.1和R.sup.2独立选择自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 araalkyl，苯基，可选地被1到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的基团取代；R.sup.3为H，C.sub.1-C.sub.6烷基，烯丙基，苄基或可选地被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，可选地被F取代的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 aralkyl，其中芳基基团可选地被1到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的基团取代；C.sub.3-C.sub.6烯基或炔基，C.sub.1-C.sub.3全氟烷基，可选地被1到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的基团取代的苯基；五氟苯基，可选地被1到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的基团取代的苄基；2-，3-或4-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，可选地被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，可选地被1到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的基团取代的苯基，五氟苯基，可选地被1到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的基团取代的苄基；R.sup.7和R.sup.8独立选择自H或C.sub.1-C.sub.4烷基；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，或其药学上可接受的盐。
• Chemokine receptor binding heterocyclic compounds
  申请人：——

  公开号：US20040220207A1

  公开（公告）日：2004-11-04

  Novel compounds that are useful for targeting chemokine receptors are disclosed. These compounds are complex tertiary amines.

  本发明揭示了用于靶向趋化因子受体的新化合物。这些化合物是复杂的三级胺。
• 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。
• Impact of Heterocycle Annulation on NIR Absorbance in Quinoid Thioacene Derivatives
  作者：Peng Hou、Sebastian Peschtrich、Nils Huber、Wolfram Feuerstein、Angela Bihlmeier、Ivo Krummenacher、Roland Schoch、Wim Klopper、Frank Breher、Jan Paradies

  DOI：10.1002/chem.202200478

  日期：2022.4.22

  quinoids display strong absorption in the NIR region between 678 and 819 nm. The dithieno[3,2-b:2',3'-d]thiophene and the thieno[2',3':4,5]thieno[3,2-b]thieno[2,3-d]thiophene derivatives were EPR active at room temperature. For the latter, variable-temperature EPR spectroscopy revealed the presence of a thermally accessible triplet state, with a singlet-triplet separation of 14.1 kJ mol-1 .

  描述了一系列醌类含硫咪唑基取代杂并苯的同系物的合成和表征。通过紫外/可见光、荧光和 EPR 光谱以及量子化学计算研究了其光电和磁性能，并与相应的苯并同系物进行了比较。室温和大气稳定的醌型化合物在 678 至 819 nm 之间的近红外区域显示出强吸收。二噻吩并[3,2-b:2',3'-d]噻吩和噻吩并[2',3':4,5]噻吩并[3,2-b]噻吩并[2,3-d]噻吩衍生物EPR 在室温下具有活性。对于后者，变温 EPR 光谱揭示了热可接近三重态的存在，单重态-三重态分离为 14.1 kJ mol-1 。