4,5-双(4-甲氧基苯基)-1,3-二氢咪唑-2-硫酮 | 39908-69-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4,5-双(4-甲氧基苯基)-1,3-二氢咪唑-2-硫酮
• 英文名称: 2-mercapto-4,5-bis(4-methoxyphenyl)imidazole
• 英文别名: 4,5-Bis(4-methoxyphenyl)-imidazol-2-thiol；4,5-bis(4-methoxyphenyl)-1H-imidazole-2-thiol；4,5-Dianisyl-2-mercaptoimidazole；2-Mercapto-4,5-di-p-anisyl-imidazol；4,5-bis-(4-methoxy-phenyl)-1,3-dihydro-imidazole-2-thione；4,5-bis(4-methoxyphenyl)-2-mercapto-1H-imidazole；4,5-bis(4-methoxyphenyl)-2-mercaptoimidazole；4,5-bis(p-methoxyphenyl)-2-mercaptoimidazole；4,5-bis(p-anisyl)-2-mercaptoimidazole；4,5-bis(4-methoxyphenyl)-1,3-dihydroimidazole-2-thione
• CAS: 39908-69-5
• 化学式: C₁₇H₁₆N₂O₂S
• mdl: MFCD00225395
• 分子量: 312.392
• InChiKey: NZKLDYYRLVFZCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.117
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  4,5-双(4-甲氧基苯基)-1,3-二氢咪唑-2-硫酮 在 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 为溶剂， 生成 [4,5-bis(4-methoxyphenyl)-2-imidazolyl]-3-thiopropenoic acid ethyl ester
  参考文献：
  名称：

  Antiinflammatory-4,5-diphenyl-2-substituted-thio-imidazoles and their

  摘要：

  咪唑衍生物的化学式为##STR1##其中Ar.sub.1和Ar.sub.2均为苯基；苯基被卤素、C.sub.1-4烷基、C.sub.1-4烷氧基或C.sub.2-6二烷基氨基取代；吡啶基；呋喃基；或噻吩基；但Ar.sub.1和Ar.sub.2不能都是未取代的苯基；R.sub.1为氢、C.sub.1-4烷基或C.sub.1-4烷基被羟基、C.sub.1-4烷氧基或C.sub.1-6烷酰氧基取代；n为0、1或2；Z为C.sub.2-6-烷基或-烯基残基，被一个或两个羟基、C.sub.1-4烷氧基、C.sub.2-8烷二氧基、C.sub.1-6烷酰氧基或苯甲酰氧基取代，或者被一个烷氧羰基基团取代；以及其与生理上可接受的酸形成的盐具有有价值的药理学性质。

  公开号：

  US04269847A1
• 作为产物：
  描述：

  4-甲氧基苯甲醛 在 potassium cyanide 、 水 作用下， 以 甲醇 、 正丁醇 为溶剂， 生成 4,5-双(4-甲氧基苯基)-1,3-二氢咪唑-2-硫酮
  参考文献：
  名称：

  Synthesis and SAR study of 4,5-diaryl-1H-imidazole-2(3H)-thione derivatives, as potent 15-lipoxygenase inhibitors

  摘要：

  A series of 4,5-diaryl-1H-imidazole-2(3H)-thione was synthesized and their inhibitory potency against soybean 15-lipoxygenase and free radical scavenging activities were determined. Compound 11 showed the best IC50 for 15-LOX inhibition (IC50 = 4.7 mu M) and free radical scavenging activity (IC50 = 14 mu M). Methylation of SH at C-2 position of imidazole has dramatically decreased the 15-LOX inhibition and radical scavenging activity as it can be observed in the inactive compound 14 (IC50 >250 mu M). Structure activity similarity (SAS) showed that the most important chemical modification in this series was methylation of SH group and Docking studies revealed a proper orientation for SH group towards Fe core of the 15-LOX active site. Therefore it was concluded that iron chelating could be a possible mechanism for enzyme inhibition in this series of compounds. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.050

文献信息

• Antiinflammatory imidazole derivatives
  申请人：Schering Aktiengesellschaft

  公开号：US04402960A1

  公开（公告）日：1983-09-06

  Imidazole derivatives of the formula ##STR1## wherein AR.sub.1 and AR.sub.2 each independently is phenyl, optionally substituted by halogen atoms, alkyl residues, alkoxy residues; or dialkylamino residues; pyridyl, furyl; or thienyl; R.sub.1 is hydrogen; alkyl of 1-6 carbon atoms optionally substituted by hydroxy groups, alkoxy groups, or acyloxy groups; benzyl; tetrahydropyran-2-yl; or tetrahydrofuran-2-yl; n is 0, 1 or 2; and Z is phenyl optionally substituted by halogen atoms, alkyl groups, alkoxy groups, nitro groups, amino, acylamino groups or trifluoromethyl groups; pyridyl; N-oxypyridyl; pyrimidinyl; thiazolyl; or thienyl, and the physiologically acceptable salts thereof with acids, have valuable pharmacological activity, e.g., antiinflammatory activity.

  咪唑衍生物的化学式为##STR1##其中AR.sub.1和AR.sub.2各自独立地是苯基，可以选择地被卤原子，烷基残基，烷氧基残基; 或二烷基氨基残基; 吡啶基，呋喃基; 或噻吩基; R.sub.1是氢; 1-6个碳原子的烷基，可以选择地被羟基，烷氧基或酰氧基取代; 苄基; 四氢吡喃-2-基; 或四氢呋喃-2-基; n为0, 1或2; Z是苯基，可以选择地被卤原子，烷基，烷氧基，硝基，氨基，酰胺基或三氟甲基取代; 吡啶基; N-氧基吡啶基; 嘧啶基; 噻唑基; 或噻吩基，以及其与酸形成的生理上可接受的盐具有有价值的药理活性，例如抗炎活性。
• Imidazoles for the treatment of atherosclerosis
  申请人：The Du Pont Merck Pharmaceutical Company

  公开号：US05310748A1

  公开（公告）日：1994-05-10

  Disclosed are imidazoles as inhibitors of acylCoA:cholesterol acyltransferase (ACAT), processes for their preparation, pharmaceutical compositions, and their use as antihypercholesterolemics and/or antiatherosclerotics.

  揭示了咪唑类化合物作为酰辅酶A：胆固醇酰基转移酶（ACAT）的抑制剂，以及它们的制备方法、药物组合物，以及作为抗高胆固醇和/或抗动脉粥样硬化药物的用途。
• 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。
• Acyl-CoA: cholesterol O-acyl transferase (ACAT) inhibitors. 1. 2-(Alkylthio)-4,5-diphenyl-1H-imidazoles as potent inhibitors of ACAT
  作者：Neil V. Harris、Andrew W. Bridge、Raymond C. Bush、Edward C. J. Coffee、Donald I. Dron、Mark F. Harper、Michael J. Ashton、David J. Lythgoe、Christopher Smith

  DOI：10.1021/jm00101a016

  日期：1992.11

  potent, bioavailable ACAT inhibitor may have beneficial effects in the treatment of atherosclerosis by (i) reducing the absorption of dietary cholesterol, (ii) reducing the secretion of very low density lipoproteins into plasma from the liver, and (iii) preventing the transformation of arterial macrophages into foam cells. We have found that a mevalonate derivative 2, which contains a 4,5-diphenyl-1H-imidazol-2-yl

  生物有效的有效ACAT抑制剂可通过（i）减少饮食中胆固醇的吸收，（ii）减少极低密度脂蛋白从肝脏向血浆的分泌以及（iii）防止转化而对动脉粥样硬化产生有益作用巨噬细胞进入泡沫细胞。我们已经发现，含有4,5-二苯基-1H-咪唑-2-基部分的甲羟戊酸酯衍生物2在体外抑制大鼠肝微粒体ACAT，并在胆固醇喂养的大鼠中产生明显的降胆固醇作用。2的类似物的结构活性关系表明，4,5-二苯基-1H-咪唑部分是抑制大鼠微粒体ACAT的药效基团。
• Pharmacologically active 4,5-diaryl-2-substituted-imidazoles
  申请人：Schering, Aktiengesellschaft

  公开号：US04272543A1

  公开（公告）日：1981-06-09

  Imidazole derivatives of the formula ##STR1## wherein AR.sub.1 and AR.sub.2 are independently each phenyl; phenyl substituted by halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy or C.sub.2-6 dialkylamino; pyridyl; furyl; or thienyl; with the proviso that AR.sub.1 and AR.sub.2 are not both unsubstituted phenyl; R.sub.1 is hydrogen, alkyl of 1-4 carbon atoms or alkyl of 1-4 carbon atoms substituted by hydroxy, C.sub.1-4 alkoxy or C.sub.1-6 alkanoyloxy; n is 0, 1 or 2; and Z is cyano; alkynyl of 2-6 carbon atoms; cycloalkyl of 3-8 carbon atoms; cycloalkyl of 3-8 carbon atoms substituted by hydroxy, acyloxy, hydroxymethyl or acyloxymethyl, "acyl" in both cases being the acyl group of a hydrocarbon, aliphatic C.sub.1-6 carboxylic acid or of benzoic acid; or alkyl of 1-4 carbon atoms substituted by cyano, phenyl or cycloalkyl of 3-6 carbon atoms; or physiologically acceptable salts thereof with an acid, have valuable pharmacological properties.

  咪唑衍生物的化学式为##STR1##其中AR.sub.1和AR.sub.2分别独立为苯基；苯基被卤素、C.sub.1-4烷基、C.sub.1-4烷氧基或C.sub.2-6二烷基氨基取代；吡啶基；呋喃基；或噻吩基；但AR.sub.1和AR.sub.2不能同时为未取代的苯基；R.sub.1为氢、1-4碳原子的烷基或被羟基、C.sub.1-4烷氧基或C.sub.1-6烷酰氧基取代的1-4碳原子的烷基；n为0、1或2；Z为氰基；2-6碳原子的炔基；3-8碳原子的环烷基；3-8碳原子的环烷基，被羟基、酰氧基、羟甲基或酰氧甲基取代，这两种情况下的"酰基"均为烃、脂肪C.sub.1-6羧酸或苯甲酸的酰基；或被氰基、苯基或3-6碳原子的环烷基取代的1-4碳原子的烷基；或其与酸形成的生理上可接受的盐具有有价值的药理学性质。