2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanone | 337536-18-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanone
• 英文别名: 2-methyl-1-(1-trityl-1H-imidazol-4-yl)propan-1-one；isopropyl(1-trityl-1H-imidazol-4-yl)ketone；2-methyl-1-(1-tritylimidazol-4-yl)propan-1-one
• CAS: 337536-18-2
• 化学式: C₂₆H₂₄N₂O
• 分子量: 380.489
• InChiKey: WUNZCWYFDRPACL-UHFFFAOYSA-N

物化性质

• 沸点：
  523.8±45.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanone 在 正丁基锂 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.25h， 生成 4-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]phenylboronic acid
  参考文献：
  名称：

  17,20-裂解酶抑制剂。第3部分：作为新型17,20-裂解酶抑制剂的联苯基甲基甲基咪唑衍生物的设计，合成和结构-活性关系

  摘要：

  合成了一系列新颖的联苯甲酰基甲基咪唑衍生物和相关化合物，作为类固醇激素生产中的关键酶17,20-裂合酶的抑制剂，并对其生物学活性进行了评估。为了确定17,20-裂解酶对相关CYP3A4酶的有效和选择性抑制剂，使用哺乳动物CYP2C5酶的X射线晶体学结构开发了人17,20-裂解酶的同源性模型。借助分子建模，对联苯部分进行了优化，得到了乙酰胺衍生物，将其通过HPLC拆分，得到了活性（-）-对映异构体。所获得的活性对映异构体不仅显示出对大鼠和人的17,20-裂合酶均具有有效的抑制作用，且IC 50值分别为14和26 nM，但对CYP3A4抑制17,20-裂解酶的选择性也极好（> 300倍）。此外，单只口服给药后，该活性对映异构体可显着降低猴子模型中的血清睾丸激素和DHEA浓度。活性对映体的不对称合成也通过使用非对映选择性格氏反应的手性中间体进行。

  DOI：

  10.1016/j.bmc.2011.02.009
• 作为产物：
  描述：

  三苯基氯甲烷 、 1-(1H-咪唑-5-基)-2-甲基丙烷-1-酮 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 以86%的产率得到2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanone
  参考文献：
  名称：

  A Concise Synthesis of Racemic 1-(6,7-Dimethoxy-2-naphthyl)-1-(1H-imidazol-4-yl)-2-methylpropan-1-ol for a Potent C₁₇,₂₀-Lyase Inhibitor

  摘要：

  The development of a practical and scaleable synthesis of 1-(6,7-dimethoxy-2-naphthyl)-1-(1H-imidazol-4-yl)-2-methylpropan-1-ol (2) is described. Racemate 2 was synthesized from commercially available 4(5)-imidazolecarboxyaldehyde (7) in three steps excluding chromatography. 4(5)-Cyanoimidazole (10) was prepared from 7 in good yield in a one-pot reaction. A Grignard reaction of cyanoimidazole 10 with isopropylmagnesium bromide followed by the addition of aqueous sulfuric acid formed acylimidazole 9. The final racemate 2 was obtained by the direct Grignard reaction of acylimidazole 9 without N-protection. This process was accomplished efficiently to produce 2 in 70% overall yield from 7 in a large-scale synthesis.

  DOI：

  10.1021/op060171+

文献信息

• 1-substituted phenyl-1-(1h-imidazol-4-yl) alcohols, process for producing the same and use thereof
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06518257B1

  公开（公告）日：2003-02-11

  To provide a composition having a steroid C17,20-lyase inhibitory activity and useful as an agent for the prophylaxis or treatment of prostatism and tumors such as breast cancer. A compound represented by the formula: wherein R is a hydrogen atom or a protecting group, R1 is a lower alkyl group or a cyclic hydrocarbon group, R2 is an aromatic hydrocarbon group optionally having substituents or an aromatic heterocyclic group optionally having substituents, R3 is a hydrocarbon group optionally having substituents, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom, and n is an integer of 0 to 4, and a salt thereof have a steroid C17,20-lyase inhibitory activity, and are useful as an agent for the pophylaxis or treatment of prostatism and tumors such as beast cancer and the like.

  提供一种具有类固醇C17,20-裂解酶抑制活性的化合物，并且作为预防或治疗前列腺增生和乳腺癌等肿瘤的药物。所述化合物的结构式如下：其中R为氢原子或保护基，R1为较低的烷基或环烃基，R2为芳香烃基，可选择地具有取代基，或芳香杂环基，可选择地具有取代基，R3为烃基，可选择地具有取代基，羟基，可选择地具有取代基，硫醇基，可选择地具有取代基，氨基，可选择地具有取代基，酰基或卤原子，n为0到4的整数，以及其盐具有类固醇C17,20-裂解酶抑制活性，并且作为预防或治疗前列腺增生和乳腺癌等肿瘤的药物。
• Highly Enantioselective Reformatsky Reaction of Ketones:  Chelation-Assisted Enantioface Discrimination
  作者：Akio Ojida、Toru Yamano、Naohiro Taya、Akihiro Tasaka

  DOI：10.1021/ol0263189

  日期：2002.9.1

  [reaction: see text] Highly enantioselective Reformatsky reaction of ketones was accomplished using cinchona alkaloids as chiral ligands. Chelation with the sp(2)-nitrogen adjacent to the reactive carbonyl center contributed the enantioface discrimination for the high enantioselectivities.

  [反应：见正文]使用金鸡纳生物碱作为手性配体可完成酮的高度对映选择性Reformatsky反应。与邻近反应性羰基中心的sp（2）-氮的螯合为高对映选择性提供了对映体鉴别。
• Process for production of optically active compounds
  申请人：Yamano Toru

  公开号：US20050107433A1

  公开（公告）日：2005-05-19

  The present invention provides a method for producing an optically active β-hydroxy ester compound represented by the general formula: wherein R 1 represents an optionally substituted hydrocarbon group and the like, R 2 represents a nitrogen-containing heterocyclic group different from R 1 , which is represented by the general formula: wherein the ring may be substituted and the like, R 3 represents an optionally substituted hydrocarbon group and the like, R 4 and R 5 represent, the same or different, a hydrogen atom, a halogen atom and the like, the symbol “*” represents an optically active center, which comprises reacting in the presence of a cinchona alkaloid and the like a compound represented by the general formula: wherein R 1 and R 2 are as defined above with a compound represented by the general formula: wherein R 3 , R 4 and R 5 are as defined above, and X is a halogen atom.

  本发明提供了一种制备光学活性β-羟基酯化合物的方法，该化合物由下式表示： 其中，R1代表可选取代的烃基等；R2代表与R1不同的含氮杂环基团，由下式表示： 其中，环可能被取代等；R3代表可选取代的烃基等；R4和R5代表相同或不同的氢原子、卤素原子等；符号“*”代表光学活性中心。该方法包括在奎宁生物碱等存在下，将下式化合物： 其中，R1和R2如上所定义，与下式化合物： 其中，R3、R4和R5如上所定义，X为卤素原子，反应。
• Imidazole derivatives, process for their preparation and their use
  申请人：——

  公开号：US20040024039A1

  公开（公告）日：2004-02-05

  The present invention provides a compound having a steroid C 17,20 -lyase inhibitory activity, which is useful as a prophylactic or therapeutic agent of prostatism and tumor such as breast cancer and the like. A compound represented by the formula: 1 wherein R is a hydrogen atom or a protecting group, R 1 is a lower alkyl group or a cyclic alkyl group, and ring A and ring B are each an optionally substituted 5-membered or 6-membered ring having an amide bond in the ring, or a salt thereof.

  本发明提供了一种具有类固醇C17,20-裂解酶抑制活性的化合物，该化合物可用作前列腺增生和乳腺癌等肿瘤的预防或治疗剂。该化合物由以下式表示：1其中R是氢原子或保护基，R1是较低的烷基或环烷基，环A和环B分别是具有环中酰胺键的可选取代的5-或6-成员环，或其盐。
• Method for producing optically active compound
  申请人：Yamano Toru

  公开号：US20060229457A1

  公开（公告）日：2006-10-12

  The present invention provides a method for producing an optically active β-hydroxy ester compound represented by the general formula: wherein R 1 represents an optionally substituted hydrocarbon group and the like, R 2 represents a nitrogen-containing heterocyclic group different from R 1 , which is represented by the general formula: wherein the ring may be substituted and the like, R 3 represents an optionally substituted hydrocarbon group and the like, R 4 and R 5 represent, the same or different, a hydrogen atom, a halogen atom and the like, the symbol “*” represents an optically active center, which comprises reacting in the presence of a cinchona alkaloid and the like a compound represented by the general formula: wherein R 1 and R 2 are as defined above with a compound represented by the general formula: wherein R 3 , R 4 and R 5 are as defined above, and X is a halogen atom.

  本发明提供一种制备光学活性β-羟基酯化合物的方法，所述化合物由下述通式表示：其中，R1表示可选取代的碳氢基团等，R2表示不同于R1的含氮杂环基团，其由下述通式表示：其中，环可能被取代等，R3表示可选取代的碳氢基团等，R4和R5表示相同或不同的氢原子、卤素原子等，“*”符号表示光学活性中心，该方法包括在奎宁生物碱等存在下将下述通式表示的化合物与下述通式表示的化合物反应：其中，R1和R2如上所定义，R3、R4和R5如上所定义，X为卤素原子。