(E)-ethyl 3-(3-bromo-5-methoxyphenyl)acrylate | 1426838-82-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-ethyl 3-(3-bromo-5-methoxyphenyl)acrylate
• 英文别名: 3-(5-bromo-3-methoxy-phenyl)thioacrylic acid S-ethyl ester；ethyl (E)-3-(3-bromo-5-methoxyphenyl)acrylate；ethyl (E)-3-(3-bromo-5-methoxyphenyl)prop-2-enoate
• CAS: 1426838-82-5
• 化学式: C₁₂H₁₃BrO₃
• 分子量: 285.137
• InChiKey: HOKHCMUHTZMXDT-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-ethyl 3-(3-bromo-5-methoxyphenyl)acrylate 在 sodium acetate 、 二异丁基氢化铝 、 对甲苯磺酰肼 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 26.0h， 生成 3-(3-bromo-5-methoxyphenyl)propanal
  参考文献：
  名称：

  The Garuganin and Garugamblin Diarylether Heptanoids: Total Synthesis and Determination of Chiral Properties Using Dynamic NMR

  摘要：

  The synthesis of the garuganin and garugamblin diarylether heptanoids using an intramolecular Ullmann coupling is reported. Alkene stereoisomers, vinylogous ester regioisomers, and beta-diketone congeners are also synthesized. The chiral properties and free energies of activation for racemization of the garuganin and garugamblin diarylether heptanoids and congeners are determined using dynamic NMR methods. A combination of techniques including coalescence measurements, line shape analysis, and selective inversion experiments are used to measure racemization barriers. None of the garuganin or garugamblin diarylether heptanoids are chiral, despite their reported specific rotation values.

  DOI：

  10.1021/jo400157d
• 作为产物：
  描述：

  3-溴-5-甲氧基苯甲醛 、 alkaline earth salt of/the/ methylsulfuric acid 在 4-二甲氨基吡啶 作用下， 以 甲苯 为溶剂， 反应 14.0h， 以97%的产率得到(E)-ethyl 3-(3-bromo-5-methoxyphenyl)acrylate
  参考文献：
  名称：

  Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus

  摘要：

  While antifolates such as Bactrim (trimethoprim-sulfamethoxazole; TMP-SMK) continue to play an important role in treating community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), resistance-conferring mutations, specifically F98Y of dihydrofolate reductase (DHFR), have arisen and compromise continued use. In an attempt to extend the lifetime of this important class, we have developed a class of propargyl-linked antifolates (PLAs) that exhibit potent inhibition of the enzyme and bacterial strains. Probing the role of the configuration at the single propargylic stereocenter in these inhibitors required us to develop a new approach to nonracemic 3-aryl-l-butyne building blocks by the painvise use of asymmetric conjugate addition and aldehyde dehydration protocols. Using this new route, a series of nonracemic PLA inhibitors was prepared and shown to possess potent enzyme inhibition (IC50 values <50 nM), antibacterial effects (several with MIC values <1 mu g/mL) and to form stable ternary complexes with both wild-type and resistant mutants. Unexpectedly, crystal structures of a pair of individual enantiomers in the wild-type DHFR revealed that the single change in configuration of the stereocenter drove the selection of an alternative NADPH cofactor, with the minor a-anomer appearing with R-27. Remarkably, this cofactor switching becomes much more prevalent when the F98Y mutation is present. The observation of cofactor site plasticity leads to a postulate for the structural basis of TMP resistance in DHFR and also suggests design strategies that can be used to target these resistant enzymes.

  DOI：

  10.1021/jacs.5b01442

文献信息

• Propionic Acid Derivatives and Methods of Use Thereof
  申请人：Biediger Ronald J.

  公开号：US20180312523A1

  公开（公告）日：2018-11-01

  Provided herein are compounds and pharmaceutical compositions of formula I where R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as described herein. Also provided pharmaceutically acceptable salts or stereoisomers of these compounds. In addition methods are provided for inhibiting the binding of an integrin to treat various pathophysiological conditions.

  本文提供了公式I的化合物和药物组合物，其中R1、R2、R3、R4、R5和R6如本文所述。还提供了这些化合物的药用可接受盐或立体异构体。此外，还提供了用于抑制整合素结合以治疗各种病理生理条件的方法。
• Propionic acid derivatives and methods of use thereof
  申请人：Biediger Ronald J.

  公开号：US10875875B2

  公开（公告）日：2020-12-29

  Provided herein are compounds and pharmaceutical compositions of formula I where R1, R2, R3, R4, R5 and R6 are as described herein. Also provided pharmaceutically acceptable salts or stereoisomers of these compounds. In addition methods are provided for inhibiting the binding of an integrin to treat various pathophysiological conditions.

  本文提供了式 I 的化合物和药物组合物 其中 R1、R2、R3、R4、R5 和 R6 如本文所述。还提供了这些化合物的药学上可接受的盐或立体异构体。此外，还提供了抑制整合素结合以治疗各种病理生理状况的方法。
• Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in <i>S</i>. <i>aureus</i>
  作者：Santosh Keshipeddy、Stephanie M. Reeve、Amy C. Anderson、Dennis L. Wright

  DOI：10.1021/jacs.5b01442

  日期：2015.7.22

  While antifolates such as Bactrim (trimethoprim-sulfamethoxazole; TMP-SMK) continue to play an important role in treating community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), resistance-conferring mutations, specifically F98Y of dihydrofolate reductase (DHFR), have arisen and compromise continued use. In an attempt to extend the lifetime of this important class, we have developed a class of propargyl-linked antifolates (PLAs) that exhibit potent inhibition of the enzyme and bacterial strains. Probing the role of the configuration at the single propargylic stereocenter in these inhibitors required us to develop a new approach to nonracemic 3-aryl-l-butyne building blocks by the painvise use of asymmetric conjugate addition and aldehyde dehydration protocols. Using this new route, a series of nonracemic PLA inhibitors was prepared and shown to possess potent enzyme inhibition (IC50 values <50 nM), antibacterial effects (several with MIC values <1 mu g/mL) and to form stable ternary complexes with both wild-type and resistant mutants. Unexpectedly, crystal structures of a pair of individual enantiomers in the wild-type DHFR revealed that the single change in configuration of the stereocenter drove the selection of an alternative NADPH cofactor, with the minor a-anomer appearing with R-27. Remarkably, this cofactor switching becomes much more prevalent when the F98Y mutation is present. The observation of cofactor site plasticity leads to a postulate for the structural basis of TMP resistance in DHFR and also suggests design strategies that can be used to target these resistant enzymes.
• The Garuganin and Garugamblin Diarylether Heptanoids: Total Synthesis and Determination of Chiral Properties Using Dynamic NMR
  作者：Zhi-Qiang Zhu、M. Quamar Salih、Edward Fynn、Alex D. Bain、Christopher M. Beaudry

  DOI：10.1021/jo400157d

  日期：2013.4.5

  The synthesis of the garuganin and garugamblin diarylether heptanoids using an intramolecular Ullmann coupling is reported. Alkene stereoisomers, vinylogous ester regioisomers, and beta-diketone congeners are also synthesized. The chiral properties and free energies of activation for racemization of the garuganin and garugamblin diarylether heptanoids and congeners are determined using dynamic NMR methods. A combination of techniques including coalescence measurements, line shape analysis, and selective inversion experiments are used to measure racemization barriers. None of the garuganin or garugamblin diarylether heptanoids are chiral, despite their reported specific rotation values.