1-(1H-咪唑-4-基)-1-(6-甲氧基萘-2-基)-2-甲基-1-丙醇 | 247173-05-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 1-(1H-咪唑-4-基)-1-(6-甲氧基萘-2-基)-2-甲基-1-丙醇
• 英文名称: 1-(1H-Imidazol-4-yl)-1-(6-methoxynaphthalen-2-yl)-2-methyl-1-propanol
• 英文别名: 1-(6-methoxy-2-naphthyl)-1-(1H-imidazol-4-yl)-2-methylpropan-1-ol；1-(1H-imidazol-4-yl)-1-(6-methoxynaphthalen-2-yl)-2-methylpropanol；1-(1H-imidazol-5-yl)-1-(6-methoxynaphthalen-2-yl)-2-methylpropan-1-ol
• CAS: 247173-05-3；336102-62-6
• 化学式: C₁₈H₂₀N₂O₂
• 分子量: 296.369
• InChiKey: FJJLMFGGWNDUMR-UHFFFAOYSA-N

物化性质

• 熔点：
  171-172 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  552.6±40.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  58.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  溴甲基乙酸酯 、 1-(1H-咪唑-4-基)-1-(6-甲氧基萘-2-基)-2-甲基-1-丙醇 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 1-(1-Acetoxymethyl-1H-imidazol-4-yl)-1-(6-methoxynaphthalen-2-yl)-2-methyl-1-propanol
  参考文献：
  名称：

  Naphthalene derivatives, their production and use

  摘要：

  包含以下公式化合物的组合物： 其中A是可被取代的含氮杂环基团，R1是氢原子、可被取代的烃基团或可被取代的单环芳族杂环基团，R2是氢原子或可被取代的低级烷基团，R3、R4、R5、R6、R7、R8和R9独立地是氢原子、可被取代的烃基团、可被取代的羟基、可被取代的硫醇基、可被取代的氨基、酰基或卤素原子，其盐或前药对类固醇C17,20-裂解酶具有抑制作用，并且对于例如预防治疗原发恶性肿瘤、其转移和复发等是有用的。

  公开号：

  US06573289B1
• 作为产物：
  描述：

  (6-methoxy-2-naphthyl)-(1-trityl-1H-imidazol-4-yl)ketone 在 甲酸 作用下， 以 四氢呋喃 为溶剂， 生成 1-(1H-咪唑-4-基)-1-(6-甲氧基萘-2-基)-2-甲基-1-丙醇
  参考文献：
  名称：

  C17,20-lyase inhibitors. Part 2: Design, synthesis and structure–activity relationships of (2-naphthylmethyl)-1H-imidazoles as novel C17,20-lyase inhibitors

  摘要：

  A series of 1- and 4-(2-naphthylmethyl)-1H-imidazoles (3 and 4) has been synthesized and evaluated as C-17,C-20-lyase inhibitors. Several 6-methoxynaphthyl derivatives showed potent C-17,C-20-lyase inhibition, suppression of testosterone biosynthesis in rats and reduction in the weight of prostate and seminal vesicles in rats, whereas most of these compounds increased the liver weight after consecutive administrations. The effect on the liver weight was removed by incorporation of a hydroxy group and an isopropyl group at the methylene bridge, as seen in (S)-28d and (S)-42. Selectivity for C-17,C-20-lyase over 11beta-hydroxylase is also discussed, and (S)-42 was found to be a more than 260-fold selective inhibitor. Furthermore, (S)-42 showed a potent suppression of testosterone biosynthesis after a single oral administration in monkeys. These data suggest that (S)-42 may be a promising agent for the treatment of androgen-dependent prostate cancer. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.016

文献信息

• PROCESS FOR THE PREPARATION OF IMIDAZOLE DERIVATIVES
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1193258A1

  公开（公告）日：2002-04-03

  The present invention provides an industrially advantageous production method of compound (V) having a steroid C17,20 lyase inhibitory action, which affords this compound in a high yield with a less number of steps without using a heavy metal compound: wherein ring A is an optionally substituted imidazole ring, R is an optionally substituted hydrocarbon group or a heterocyclic group, and R1, R2, R3, R4, R5, R6 and R7 are each a hydrogen atom, an optionally substituted hydrocarbon group, OH, SH or NH2, an acyl group or a halogen and the like.

  本发明提供了一种在不使用重金属化合物的情况下，以较少的步骤高产率地制备具有类固醇C17,20裂解酶抑制作用的化合物（V）的工业上有利的生产方法：其中环A是一个可选择取代的咪唑环，R是一个可选择取代的碳氢化合物基团或杂环基团，R1、R2、R3、R4、R5、R6和R7分别是氢原子、可选择取代的碳氢化合物基团、羟基、硫氢基或氨基、酰基或卤素等。
• Process for producing optically active naphthalene derivative and optical resolver therefor
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06800778B1

  公开（公告）日：2004-10-05

  The present invention provides a method of producing an optically active form of a compound represented by the formula (I) having a steroid C17,20-lyase inhibitory activity and is useful as an agent for the prophylaxis or treatment of prostatism, tumor such as breast cancer, and the like or a salt thereof, which method includes reacting a mixture of optically active compounds of a naphthalene derivative represented by the formula: wherein R is a nitrogen-containing heterocyclic group, R1 is a hydrogen atom, a hydrocarbon group or an aromatic heteromonocyclic group, R2 is a hydrogen atom or a lower alkyl group, * shows the position of an asymmetric carbon, R3, R4, R5, R6, R7, R8 and R9 are each independently a hydrogen atom, a hydrocarbon group, a hydroxy group, a thiol group, an amino group, a carbamoyl group, an acyl group or a halogen atom, and R7 is bonded with R6 or R8 to form, together with a carbon atom on a naphthalene ring, a 5 or 6-membered ring containing an oxygen atom, with an optically active form of a compound represented by the formula: wherein ring A is a benzene ring, R10 and R11 are the same or different and each is a hydrogen atom, a hydrocarbon group or a halogen atom, or R10 and R11 in combination show an alkylene group, * shows the position of an asymmetric carbon, and ring B and ring C are each an aromatic ring, separating the resulting salt, and isolating the optically active form, and a novel reagent for optical resolution.

  本发明提供了一种生产一种具有类固醇C17,20-裂解酶抑制活性的化合物的光学活性形式的方法，该化合物由式（I）表示，可用作预防或治疗前列腺增生、乳腺癌等肿瘤的药物或其盐。该方法包括将由式表示的萘衍生物的光学活性化合物混合物反应：其中R是含氮杂环基团，R1是氢原子、碳氢基团或芳香族杂单环基团，R2是氢原子或较低的烷基团，*表示一个不对称碳的位置，R3、R4、R5、R6、R7、R8和R9分别独立地是氢原子、碳氢基团、羟基、硫醇基、氨基、氨基甲酰基、酰基或卤素原子，其中R7与R6或R8结合，与萘环上的碳原子一起形成一个含氧原子的5或6元环。通过与由式表示的化合物的光学活性形式反应：其中环A是苯环，R10和R11相同或不同，分别是氢原子、碳氢基团或卤素原子，或R10和R11组合成一个烷基链，*表示一个不对称碳的位置，环B和环C分别是芳香环，分离得到的盐，并分离得到光学活性形式，以及用于光学分辨的新试剂。
• Process for the preparation of imidazole derivatives
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06713632B1

  公开（公告）日：2004-03-30

  A method for producing a compound of the formula: wherein R is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group and ring A is an imidazole ring which is optionally substituted further, or a salt thereof, which method comprises reacting a compound of the formula: wherein ring A is as defined above, or a salt thereof, and a compound of the formula: R—M1  (II) wherein M1 is an alkali metal atom or a group of the formula: —Mg—Y1 where Y1 is a halogen atom, and R is as defined above, or a salt thereof, and bringing the resulting product into contact with an acid.

  一种生产公式为：其中R是可选取代的烃基团或可选取代的杂环基团，环A是一种咪唑环，也可进一步取代，或其盐的化合物的方法，包括将公式为：其中环A如上所定义，或其盐，和公式为：R-M1 (II)其中M1是碱金属原子或公式为：-Mg-Y1的基团，其中Y1是卤素原子，而R如上所定义，或其盐，反应，并将所得产物与酸接触。
• A Concise Synthesis of Racemic 1-(6,7-Dimethoxy-2-naphthyl)-1-(1<i>H</i>-imidazol-4-yl)-2-methylpropan-1-ol for a Potent C₁₇,₂₀-Lyase Inhibitor
  作者：Jun-ichi Kawakami、Kazuhiro Kimura、Masayoshi Yamaoka

  DOI：10.1021/op060171+

  日期：2007.3.1

  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.
• PROCESS FOR PRODUCING OPTICALLY ACTIVE NAPHTHALENE DERIVATIVE AND OPTICAL RESOLVER THEREFOR
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1227085B1

  公开（公告）日：2006-03-15