2-trimethylsilylethyl 4-hydroxybenzoate | 176700-52-0

• 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: 2-trimethylsilylethyl 4-hydroxybenzoate
• CAS: 176700-52-0
• 化学式: C₁₂H₁₈O₃Si
• 分子量: 238.359
• InChiKey: VITTWCZAICCHBB-UHFFFAOYSA-N

物化性质

• 熔点：
  102-103 °C
• 沸点：
  334.0±22.0 °C(Predicted)
• 密度：
  1.047±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.89
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-trimethylsilylethyl 4-hydroxybenzoate 在 吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-quinoxaline-2-carboxylic acid 4-carboxy-phenyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 2-Pyrazinylcarboxamido- benzoates and β-Ionylideneacetamidobenzoates with Retinoidal Activity

  摘要：

  The structure-activity relationships of two series of novel retinoids (2-pyrazinylcarboxamidobenzoates and beta-ionylideneacetamidobenzoates) have been investigated by evaluating their ability to induce differentiation in both human promyelocytic leukemia (HL60) cells and mouse embryonal carcinoma (P19) cells. The most active compound (ED50 = 8.3 x 10(-9) M) of the 2-pyrazinylcarboxamidobenzoates is 4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylquinoxalyl)-carboxamido]benzoic acid (9u), while the most active analogue of the beta-ionylideneacetamidobenzoates is 4-[3-methyl-5-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-(2E,4E)-pentadienamido]benzoic acid (10a, ED50 = 3.2 x 10(-8) M). Our studies identify an absolute requirement for the carboxylic acid moiety on the aromatic ring to be para relative to the amide linkage for activity. Benzoate substitutions in the ortho position relative to the terminal carboxylate (9d,k,r) are well-tolerated; however, a methoxy substituent meta relative to the terminal carboxylate gives rise to only weakly active analogues (9x). Conformational studies (NMR, X-ray crystallography) of the 2-pyrazinylcarboxamidobenzoates indicate that the preferred conformation exhibits a trans-amide bond and an internal hydrogen bond between the quinoxaline N1 and HN amide which locks the torsional angle between C2 and CO in the s-trans conformation. N-Methylation (9y) results in loss of activity. Studies indicate that there is now a cis-amide bond present which redirects the carboxylate toward the pharmacophoric gem-dimethyl groups. The distance between the gem-dimethyl group and the terminal carboxylate appears to be too short to activate the retinoid receptor. N-Methylation in the beta-ionylideneacetamidobenzoate series (10c) also results in the formation of a cis-amide bond and loss of activity.

  DOI：

  10.1021/jm9801354
• 作为产物：
  描述：

  2'-(trimethylsilyl)ethyl-4-acetoxybenzoate 在 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 2-trimethylsilylethyl 4-hydroxybenzoate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 2-Pyrazinylcarboxamido- benzoates and β-Ionylideneacetamidobenzoates with Retinoidal Activity

  摘要：

  The structure-activity relationships of two series of novel retinoids (2-pyrazinylcarboxamidobenzoates and beta-ionylideneacetamidobenzoates) have been investigated by evaluating their ability to induce differentiation in both human promyelocytic leukemia (HL60) cells and mouse embryonal carcinoma (P19) cells. The most active compound (ED50 = 8.3 x 10(-9) M) of the 2-pyrazinylcarboxamidobenzoates is 4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylquinoxalyl)-carboxamido]benzoic acid (9u), while the most active analogue of the beta-ionylideneacetamidobenzoates is 4-[3-methyl-5-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-(2E,4E)-pentadienamido]benzoic acid (10a, ED50 = 3.2 x 10(-8) M). Our studies identify an absolute requirement for the carboxylic acid moiety on the aromatic ring to be para relative to the amide linkage for activity. Benzoate substitutions in the ortho position relative to the terminal carboxylate (9d,k,r) are well-tolerated; however, a methoxy substituent meta relative to the terminal carboxylate gives rise to only weakly active analogues (9x). Conformational studies (NMR, X-ray crystallography) of the 2-pyrazinylcarboxamidobenzoates indicate that the preferred conformation exhibits a trans-amide bond and an internal hydrogen bond between the quinoxaline N1 and HN amide which locks the torsional angle between C2 and CO in the s-trans conformation. N-Methylation (9y) results in loss of activity. Studies indicate that there is now a cis-amide bond present which redirects the carboxylate toward the pharmacophoric gem-dimethyl groups. The distance between the gem-dimethyl group and the terminal carboxylate appears to be too short to activate the retinoid receptor. N-Methylation in the beta-ionylideneacetamidobenzoate series (10c) also results in the formation of a cis-amide bond and loss of activity.

  DOI：

  10.1021/jm9801354

文献信息

• O- or S- substituted tetrahydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
  申请人：Allergan Sales, Inc.

  公开号：US06344561B2

  公开（公告）日：2002-02-05

  Compounds of the formula where the symbols have the meaning described in the application, have retinoid-like or retinoid antagonist-like biological activity.

  式中符号的含义如申请中所述，具有类视黄醇或类视黄醇拮抗剂样的生物活性。
• Mild deprotection of 2-(trimethylsilyl)ethyl esters
  作者：Michael H Serrano-Wu、Alicia Regueiro-Ren、Denis R St. Laurent、Tina M Carroll、Balu N Balasubramanian

  DOI：10.1016/s0040-4039(01)01859-7

  日期：2001.12

  A method for the deprotection of 2-(trimethylsilyl)ethyl (TMSE) esters is described. Treatment of carboxylic esters with NaH in DMF cleanly produces the deprotected acid after extractive work-up. This method can be applied to sterically-hindered substrates as well as esters containing fluoride-labile functionality. A tandem alkylation/ester deprotection procedure is also presented.

  描述了使2-（三甲基甲硅烷基）乙基（TMSE）酯脱保护的方法。在萃取后，用NaH在DMF中处理羧酸酯可干净地产生脱保护的酸。该方法可应用于空间受阻的底物以及含氟不稳定官能团的酯。还提出了串联烷基化/酯脱保护的方法。
• Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
  申请人：——

  公开号：US20020173631A1

  公开（公告）日：2002-11-21

  Compounds of the formula 1 where the symbols have the meaning described in the application, have retinoid-like or retinoid antagonist-like biological activity.

  式子1中的符号所描述的化合物具有类视黄醇或类视黄醇拮抗剂类似的生物活性。
• O- or S- substituted tetrahydronaphthalene derivatives having retinoid
  申请人：ALLERGAN

  公开号：US05741896A1

  公开（公告）日：1998-04-21

  Compounds of the formula ##STR1## where the symbols have the meaning described in the application, have retinoid-like or retinoid antagonist-like biological activity.

  式子为##STR1##的化合物，其中符号的含义在申请中有描述，具有类视黄醇或类视黄醇拮抗剂的生物活性。
• Oxo-substituted tetrahydronaphthalene derivatives having retinold and/or
  申请人：Allergan

  公开号：US05747542A1

  公开（公告）日：1998-05-05

  Compounds of the formula ##STR1## where the symbols have the meaning described in the application, have retinoid-like or retinoid antagonist-like biological activity.

  式子##STR1##所表示的化合物，其中符号的含义在申请书中有描述，具有类视黄醇或类视黄醇拮抗剂样的生物活性。