(E)-ethyl 3-(4-bromo-3-methoxyphenyl)acrylate | 1352042-54-6

• 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-(4-bromo-3-methoxyphenyl)acrylate
• 英文别名: ethyl 3-(4-bromo-3-methoxyphenyl)acrylate；ethyl 4-bromo-3-methoxycinnamate；ethyl (E)-4-bromo-3-methoxycinnamate；ethyl (E)-3-(4-bromo-3-methoxyphenyl)prop-2-enoate
• CAS: 1352042-54-6
• 化学式: C₁₂H₁₃BrO₃
• 分子量: 285.137
• InChiKey: YFBFILTVAQOFBG-FNORWQNLSA-N

物化性质

• 沸点：
  362.9±27.0 °C(Predicted)
• 密度：
  1.376±0.06 g/cm3(Predicted)

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-(4-bromo-3-methoxyphenyl)acrylate 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (E)-3-(4-bromo-3-methoxyphenyl)prop-2-enal
  参考文献：
  名称：

  Synthetic and in vitro studies to indicate that the structure of the PTP1B inhibitor isolated from Acanthopanax senticosus requires reinvestigation

  摘要：

  We herein describe the syntheses of 3,5-dimethoxy-4-{2-methoxy-4-[(1E)-3-oxoprop-1-en-1-yl]phenoxy}benzaldehyde (1) (the proposed structure for the naturally occurring protein tyrosine phosphatase 1B (PTP1B) inhibitor isolated from Acanthopanax senticosus) and its three positional isomers 3, 4, and 5. The inhibitory activities of these four compounds against PTP1B were also investigated. Comparison of the spectral data for 1, 3, 4, and 5 with the data obtained for the PTP1B inhibitor isolated from A. senticosus revealed that the original structural assignment as compound 1 was incorrect. In addition, none of the above four compounds exhibited inhibitory activity against PTP1B. Based on these results, it is apparent the structure of the PTP1B inhibitor isolated from Acanthopanax senticosus requires reinvestigation.

  DOI：

  10.1016/j.phytol.2018.07.028
• 作为产物：
  描述：

  4-溴-3-甲氧基苯甲腈 在 二异丁基氢化铝 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 26.0h， 生成 (E)-ethyl 3-(4-bromo-3-methoxyphenyl)acrylate
  参考文献：
  名称：

  Analogues of Orphan Nuclear Receptor Small Heterodimer Partner Ligand and Apoptosis Inducer (E)-4-[3-(1-Adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic Acid. 2. Impact of 3-Chloro Group Replacement on Inhibition of Proliferation and Induction of Apoptosis of Leukemia and Cancer Cell Lines

  摘要：

  The parent phenol of adapalene and its (E)-cinnamic acid analogue were found to induce cancer cell apoptosis but cause adverse systemic effects when administered to mice. In contrast, their respective 5-Cl- and 3-Cl-substituted analogues had their adverse effects mitigated without a comparable loss of cancer cell inhibitory activity. As a result, pharmacologic space in this region of the cinnamic phenyl ring scaffold was explored. Various substituents were introduced, and their effects on cancer, cell proliferation and viability were evaluated. Cinnamic acids having 3-Br, CN, NO2, NH2, OMe, and N-3 groups had activity comparable to that of 4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-chlorocinnamic acid. A comparative molecular field analysis study indicated that introduction of an H-bond acceptor at position 3 of the central phenyl ring would favor inhibition of leukemia cell viability, and docking suggested its hydrogen bonding with a polar group in a small heterodimer partner homology model. The 3-CN, NO2, NH2, and OH analogues also inhibited MMTV-Wnt1 murine mammary stem cell viability.

  DOI：

  10.1021/jm2011436

文献信息

• [EN] RAB GERANYLGERANYL TRANSFERASE INHIBITORS<br/>[FR] INHIBITEURS DE LA GÉRANYLEGÉRANYLE TRANSFÉRASE VERS RAB
  申请人：LEAD DISCOVERY CENTER GMBH

  公开号：WO2015181272A1

  公开（公告）日：2015-12-03

  The present invention relates to novel Rab geranylgeranyl transferase inhibitors of general formula (I) and stereoisomeric forms, hydrates, solvates and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing at least one of said Rab geranylgeranyl transferase inhibitors together with at least one pharmaceutically acceptable carrier, excipient and/or diluent. Said Rab geranylgeranyl transferase inhibitors are particularly useful for the treatment and/or prophylaxis of proliferative diseases, tumors, cancers, metastases, diseases caused by pathological vesicle transport abnormalities, neuronal disorders (e.g. Charcotte-Marie-Tooth disease), infective diseases, thrombocytosis and clotting diseases and diseases where Rab mutations have been identified.

  本发明涉及一般式(I)及其立体异构体、水合物、溶剂化物和药学上可接受的盐的新型Rab靶向酰基转移酶抑制剂，以及至少包含其中一种Rab靶向酰基转移酶抑制剂和至少一种药学上可接受的载体、赋形剂和/或稀释剂的制药组合物。所述Rab靶向酰基转移酶抑制剂特别适用于治疗和/或预防增生性疾病、肿瘤、癌症、转移瘤、由病理性囊泡转运异常引起的疾病、神经系统疾病（如Charcotte-Marie-Tooth病）、感染性疾病、血小板增多症和凝血疾病以及已经确定存在Rab突变的疾病。
• Analogues of Orphan Nuclear Receptor Small Heterodimer Partner Ligand and Apoptosis Inducer (<i>E</i>)-4-[3-(1-Adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic Acid. 2. Impact of 3-Chloro Group Replacement on Inhibition of Proliferation and Induction of Apoptosis of Leukemia and Cancer Cell Lines
  作者：Zebin Xia、Ricardo G. Correa、Jayanta K. Das、Lulu Farhana、David J. Castro、Jinghua Yu、Robert G. Oshima、Joseph A. Fontana、John C. Reed、Marcia I. Dawson

  DOI：10.1021/jm2011436

  日期：2012.1.12

  The parent phenol of adapalene and its (E)-cinnamic acid analogue were found to induce cancer cell apoptosis but cause adverse systemic effects when administered to mice. In contrast, their respective 5-Cl- and 3-Cl-substituted analogues had their adverse effects mitigated without a comparable loss of cancer cell inhibitory activity. As a result, pharmacologic space in this region of the cinnamic phenyl ring scaffold was explored. Various substituents were introduced, and their effects on cancer, cell proliferation and viability were evaluated. Cinnamic acids having 3-Br, CN, NO2, NH2, OMe, and N-3 groups had activity comparable to that of 4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-chlorocinnamic acid. A comparative molecular field analysis study indicated that introduction of an H-bond acceptor at position 3 of the central phenyl ring would favor inhibition of leukemia cell viability, and docking suggested its hydrogen bonding with a polar group in a small heterodimer partner homology model. The 3-CN, NO2, NH2, and OH analogues also inhibited MMTV-Wnt1 murine mammary stem cell viability.
• Synthetic and in vitro studies to indicate that the structure of the PTP1B inhibitor isolated from Acanthopanax senticosus requires reinvestigation
  作者：Toshiro Noshita、Ryoya Onishi、Kaori Miura、Yoshitomo Hamada、Yuki Nishino、Hidekazu Ouchi、Akihiro Tai

  DOI：10.1016/j.phytol.2018.07.028

  日期：2018.10

  We herein describe the syntheses of 3,5-dimethoxy-4-2-methoxy-4-[(1E)-3-oxoprop-1-en-1-yl]phenoxy}benzaldehyde (1) (the proposed structure for the naturally occurring protein tyrosine phosphatase 1B (PTP1B) inhibitor isolated from Acanthopanax senticosus) and its three positional isomers 3, 4, and 5. The inhibitory activities of these four compounds against PTP1B were also investigated. Comparison of the spectral data for 1, 3, 4, and 5 with the data obtained for the PTP1B inhibitor isolated from A. senticosus revealed that the original structural assignment as compound 1 was incorrect. In addition, none of the above four compounds exhibited inhibitory activity against PTP1B. Based on these results, it is apparent the structure of the PTP1B inhibitor isolated from Acanthopanax senticosus requires reinvestigation.