乙基4-(4-甲氧基苯基)-3-氧代丁酸酯 | 32711-91-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 乙基4-(4-甲氧基苯基)-3-氧代丁酸酯
• 中文别名: 4-(4-甲氧苯基)-3-氧代丁酸乙酯；对甲氧基苯乙酰乙酸乙酯
• 英文名称: ethyl 4-(4-methoxyphenyl)-3-oxobutanoate
• CAS: 32711-91-4
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: ZZEJIZHZTDVNRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  乙基4-(4-甲氧基苯基)-3-氧代丁酸酯 在 ammonium acetate 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以85%的产率得到ethyl (2Z)-3-amino-4-(4-methoxyphenyl)but-2-enoate
  参考文献：
  名称：

  Structural Optimization and Biological Evaluation of 2-Substituted 5-Hydroxyindole-3-carboxylates as Potent Inhibitors of Human 5-Lipoxygenase

  摘要：

  Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 mu M, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 mu M) and significantly prevented leukotriene B-4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics.

  DOI：

  10.1021/jm900212y
• 作为产物：
  描述：

  对甲氧基苯乙酸 在 水 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 14.5h， 生成 乙基4-(4-甲氧基苯基)-3-氧代丁酸酯
  参考文献：
  名称：

  Acylation of Meldrum’s acid with arylacetic acid imidazolides as a convenient method for the synthesis of 4-aryl-3-oxobutanoates

  摘要：

  在 1,1′-羰基二咪唑存在下，(庚)芳基乙酸在乙醇中对 Meldrum's 酸进行 C-酰化，可高产 4-(庚)芳基-3-氧代丁酸乙酯。

  DOI：

  10.1007/s11172-011-0019-9

文献信息

• Non-metal Lewis acid-catalyzed cross-Claisen condensation for β-keto esters
  作者：Tianyu Zhang、Zhenkun Yang、Dapeng Zhou、Fuliang Meng、Zhengyu Han、Hai Huang

  DOI：10.1039/d1ob01785c

  日期：——

  In this work, we disclose a new catalytic and highly chemoselective cross-Claisen condensation of esters. In the presence of TBSNTf2 as a non-metal Lewis acid, various esters can undergo cross-Claisen condensation to form β-keto esters which are important building blocks. Compared with the traditional Claisen condensation, this process, employing silyl ketene acetals (SKAs) as carbonic nucleophiles

  在这项工作中，我们公开了一种新的催化和高度化学选择性的酯交叉克莱森缩合。在作为非金属路易斯酸的 TBSNTf 2存在下，各种酯可以进行交叉克莱森缩合以形成β-酮酯，这是重要的结构单元。与传统的克莱森缩合相比，该工艺以甲硅烷基乙烯酮缩醛（SKAs）为含碳亲核试剂实现交叉克莱森缩合，条件温和，官能团耐受性好。
• AMINOINDANE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THERAPY
  申请人：POHLKI Frauke

  公开号：US20120040948A1

  公开（公告）日：2012-02-16

  The present invention relates to aminoindane derivatives of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such aminoindane derivatives, and the use of such aminoindane derivatives for therapeutic purposes. The aminoindane derivatives are GlyT1 inhibitors.

  本发明涉及公式（I）的氨基茚衍生物或其生理耐受的盐。该发明涉及包含这种氨基茚衍生物的药物组合物，以及利用这种氨基茚衍生物进行治疗的用途。这些氨基茚衍生物是GlyT1抑制剂。
• Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
  作者：Jakob S. Pallesen、Dilip Narayanan、Kim T. Tran、Sara M. Ø. Solbak、Giuseppe Marseglia、Louis M. E. Sørensen、Lars J. Høj、Federico Munafò、Rosa M. C. Carmona、Anthony D. Garcia、Haritha L. Desu、Roberta Brambilla、Tommy N. Johansen、Grzegorz M. Popowicz、Michael Sattler、Michael Gajhede、Anders Bach

  DOI：10.1021/acs.jmedchem.0c02094

  日期：2021.4.22

  Keap1–Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220–380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic

  靶向核因子类红细胞2相关因子2（Nrf2）和与Kelch样ECH相关蛋白1（Keap1）之间的蛋白相互作用是控制涉及氧化应激疾病的潜在治疗策略。在这里，在基于片段的解构重建（FBDR）研究中，将六类已知的小分子Keap1-Nrf2 PPI抑制剂分解为77个片段，并在四个正交试验中进行了测试。这给出了17个片段命中，其中X射线晶体学显示其中6个在Keap1 Kelch结合袋中结合。相对于亲本片段，两个命中片段以220-380倍的亲和力（K i = 16μM）被合并到化合物8中。系统优化产生了一些与K i有关的新颖类似物值0.04–0.5μM，通过X射线晶体学测定的结合模式，以及增强的微粒体稳定性。这证明了FBDR如何可用于发现新的片段片段，阐明重要的配体-蛋白质相互作用以及鉴定Keap1-Nrf2 PPI的新有效抑制剂。
• Efficient Activation of Zinc: Application of the Blaise Reaction to an Expedient Synthesis of a Statin Intermediate
  作者：Hyunik Shin、No-Soo Kim、Bo Seung Choi、Ki Kon Lee、Hyeong-wook Choi、Jay Hyok Chang、Kyu Woong Lee、Do Hyun Nam

  DOI：10.1055/s-2004-831197

  日期：——

  Efficient and practical in situ zinc activation was accomplished by treatment with catalytic amount of an organic acid. The protocol was applied successfully to the Blaise reaction of various nitriles. Noteworthy is the excellent Blaise transformation of (S)-4-chloro-3-trimethylsilyloxybutyronitrile (2b) into tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate (1), a key intermediate for the preparation of HMG-CoA reductase inhibitors (statins).

  高效且实用的原位锌活化方法通过使用少量有机酸处理得以实现。该方案成功应用于多种腈的布莱斯反应。值得注意的是，(S)-4-氯-3-三甲基硅氧基丁腈 (2b) 经优异的布莱斯转化，生成叔丁基 (S)-6-氯-5-羟基-3-氧代己酸酯 (1)，这是制备HMG-CoA还原酶抑制剂（他汀类药物）的关键中间体。
• Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains
  作者：Amin Li、Yabo Ouyang、Ziyun Wang、Yuanyuan Cao、Xiangyi Liu、Li Ran、Chao Li、Li Li、Liang Zhang、Kang Qiao、Weisi Xu、Yang Huang、Zhili Zhang、Chao Tian、Zhenming Liu、Shibo Jiang、Yiming Shao、Yansheng Du、Liying Ma、Xiaowei Wang、Junyi Liu

  DOI：10.1021/jm400102x

  日期：2013.5.9

  Novel 6-substituted-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated. Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs)

  合成了新型6-取代-4-环烷氧基-吡啶-2（1 H）-ones作为非核苷类逆转录酶抑制剂（NNRTIs），并对其生物学活性进行了评估。大多数化合物，尤其是分别带有3-异丙基和3-碘基团的26和22化合物，对野生型HIV-1菌株和对逆转录酶抑制剂（RTIs）具有抗性的化合物均表现出很高的活性。的非对映体26 -反式和26 -顺式分别合成并用HPLC和NOESY谱证实。在26 -反式异构体有大约400倍比的更有效的活动26 -顺。在对26 -反式对映异构体，与EC的最有效的抑制剂之一50的75000 4纳米的和选择性指数（SI），是针对生殖道感染抗性株的单（Y181C和K103N）或双（一面板高的有效A17）逆转录酶突变。结果表明，这些新颖的吡啶酮衍生物具有作为具有改善的抗病毒效力和耐药性的新型抗逆转录病毒药物而被进一步开发的潜力。