ethyl 3-(2-bromoethoxy)benzoate | 192182-58-4

• 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: ethyl 3-(2-bromoethoxy)benzoate
• CAS: 192182-58-4
• 化学式: C₁₁H₁₃BrO₃
• 分子量: 273.126
• InChiKey: VSNPACRLJKTQBA-UHFFFAOYSA-N

物化性质

• 沸点：
  142-144 °C(Press: 0.65 Torr)
• 密度：
  1.382±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 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：

  ethyl 3-(2-bromoethoxy)benzoate 在 盐酸 、 水 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.5h， 生成 3-(2-吗啉-4-基-乙氧基)-苯甲酸
  参考文献：
  名称：

  [EN] ASK1 INHIBITING PYRROLOPYRIMIDINE DERIVATIVES
  [FR] DÉRIVÉS PYRROLOPYRIMIDINE INHIBANT ASK1

  摘要：

  这项发明涉及式(I)的吡咯吡嘧啶衍生物：其中R1、X、p、R4、R2和R3如本文所定义，并且它们作为药物的用途。

  公开号：

  WO2012080735A1
• 作为产物：
  描述：

  间羟基苯甲酸 在 氯化亚砜 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 33.0h， 生成 ethyl 3-(2-bromoethoxy)benzoate
  参考文献：
  名称：

  使用片段替代方法设计人白细胞常见抗原相关（PTP-LAR）的潜在选择性抑制剂

  摘要：

  摘要 PTP-LAR的过表达可能引起胰岛素抵抗，因此PTP-LAR可能是治疗糖尿病的有希望的靶标。在这项研究中，我们应用了具有片段替换方法的计算机建模方法，通过针对PTP域和位点B来筛选片段数据库，目的是发现有效和选择性的PTP-LAR抑制剂。获得了一系列新颖的4-噻唑烷酮衍生物。他们对ADMET的预测结果表明，这些新化合物可能成为候选药物。合成了这些衍生物的系列。随后，测定了它们对PTP-LAR的抑制活性。化合物7d对PTP-LAR（10.41μM）的选择性高于其同系物PTP1B（IC 50 = 44.40μM），SHP2（IC 50 > 122.81μM）和CDC25B（IC 50> 122.81μM）并通过对接和分子动力学模拟来提出化合物7d与PTP-LAR最可能的结合方式。因此，本文报道的发现可能为发现潜在的选择性PTP-LAR抑制剂铺平了道路。 缩略语 点对点 人白细胞常见抗原相关

  DOI：

  10.1080/07391102.2019.1699862

文献信息

• Synthesis, Biological Evaluation, and Structure−Activity Relationships of 3-Acylindole-2-carboxylic Acids as Inhibitors of the Cytosolic Phospholipase A₂
  作者：Matthias Lehr

  DOI：10.1021/jm960863w

  日期：1997.8.1

  Replacement of the carboxylic acid group in position 2 of the indole with an acetic or propionic acid substituent led to a decrease of inhibitory potency. Enzyme inhibition was optimal when the acyl residue in position 3 had a length of 12 or more carbons. Conformational restriction of the acyl residue did not influence activity. Introduction of alkyl chains at position 1 of the indole with 8 or more carbons

  制备3-酰基吲哚-2-羧酸衍生物，并评价其抑制完整牛血小板的胞质磷脂酶A2的能力。为了定义酶抑制的结构要求，对羧酸基，酰基残基和位置1的部分进行了系统修饰。此外，将不同的取代基引入到吲哚的苯基部分中。用乙酸或丙酸取代基取代吲哚的2位上的羧酸基导致抑制效力的降低。当位置3上的酰基残基具有12个或更多碳原子时，酶抑制作用最佳。酰基残基的构象限制不影响活性。在具有8个或更多个碳的吲哚的位置1处引入烷基链导致活性降低。然而，发现用羧酸部分取代此类化合物的ω-甲基会显着增加抑制效力。在测试的吲哚衍生物中，1- [2-（4-羧基苯氧基）乙基] -3-十二烷酰基吲哚-2-羧基酸（29b）具有最高的效价。IC50为0.5 microM，它的活性比标准cPLA2抑制剂花生四烯酸三氟甲基酮（IC50：11 microM）高约20倍。
• ASK 1 INHIBITING PYRROLOPYRIMIDINE DERIVATIVES
  申请人：Witty David R.

  公开号：US20140038957A1

  公开（公告）日：2014-02-06

  This invention relates to pyrrolopyrimidine derivatives of formula (I): where R 1 , X, p, R 4 , R 2 and R 3 are as defined herein, and their use as pharmaceuticals.

  本发明涉及公式（I）的吡咯吡嘧啶衍生物：其中R1、X、p、R4、R2和R3如本文所定义，并且它们作为药物的用途。
• ASK 1 inhibiting pyrrolopyrimidine derivatives
  申请人：Witty David R.

  公开号：US09045485B2

  公开（公告）日：2015-06-02

  This invention relates to pyrrolopyrimidine derivatives of formula (I): where R1, X, p, R4, R2 and R3 are as defined herein, and their use as pharmaceuticals.

  本发明涉及式（I）的吡咯吡咪啉衍生物：其中R1，X，p，R4，R2和R3如本文所定义，并且它们的用途为药物。
• 1,2,4‐Triazole‐3‐Thione Analogues with a 2‐Ethylbenzoic Acid at Position 4 as VIM‐type Metallo‐β‐Lactamase Inhibitors
  作者：Federica Verdirosa、Laurent Gavara、Laurent Sevaille、Giusy Tassone、Giuseppina Corsica、Alice Legru、Georges Feller、Giulia Chelini、Paola Sandra Mercuri、Silvia Tanfoni、Filomena Sannio、Manuela Benvenuti、Giulia Cerboni、Filomena De Luca、Ezeddine Bouajila、Yen Vo Hoang、Patricia Licznar‐Fajardo、Moreno Galleni、Cecilia Pozzi、Stefano Mangani、Jean‐Denis Docquier、Jean‐François Hernandez

  DOI：10.1002/cmdc.202100699

  日期：2022.4.5

  AbstractMetallo‐β‐lactamases (MBLs) are increasingly involved as a major mechanism of resistance to carbapenems in relevant opportunistic Gram‐negative pathogens. Unfortunately, clinically efficient MBL inhibitors still represent an unmet medical need. We previously reported several series of compounds based on the 1,2,4‐triazole‐3‐thione scaffold. In particular, Schiff bases formed between diversely 5‐substituted‐4‐amino compounds and 2‐carboxybenzaldehyde were broad‐spectrum inhibitors of VIM‐type, NDM‐1 and IMP‐1 MBLs. Unfortunately, these compounds were unable to restore antibiotic susceptibility of MBL‐producing bacteria, probably because of poor penetration and/or susceptibility to hydrolysis. To improve their microbiological activity, we synthesized and characterized compounds where the hydrazone‐like bond of the Schiff base analogues was replaced by a stable ethyl link. This small change resulted in a narrower inhibition spectrum, as all compounds were poorly or not inhibiting NDM‐1 and IMP‐1, but showed a significantly better activity on VIM‐type enzymes, with Ki values in the μM to sub‐μM range. The resolution of the crystallographic structure of VIM‐2 in complex with one of the best inhibitors yielded valuable information about their binding mode. Interestingly, several compounds were shown to restore the β‐lactam susceptibility of VIM‐type‐producing E. coli laboratory strains and also of K. pneumoniae clinical isolates. In addition, selected compounds were found to be devoid of toxicity toward human cancer cells at high concentration, thus showing promising safety.
• Design, synthesis, biological evaluation and molecular dynamics simulation studies of (R)-5-methylthiazolidin-4-One derivatives as megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2) inhibitors for the treatment of type 2 diabetes
  作者：Jingwei Wu、Yingzhan Sun、Hui Zhou、Ying Ma、Runling Wang

  DOI：10.1080/07391102.2019.1654410

  日期：2020.7.23

  PTP-MEG2 plays a significant role in insulin production and is able to enhance insulin signaling and improve insulin sensitivity. So, PTP-MEG2 inhibitors are closely associated with type 2 diabetes therapy. A series of novel (R)-5-methylthiazolidin-4-one derivatives were designed and synthesized, and their PTP-MEG2 inhibitory activities (IC50) were determined. Among the desired compounds, 1h shares the highest inhibitory activity (IC50 = 1.34 mu M) against PTP-MEG2. Additionally, various post-dynamic analyses confirmed that when compound 1h bound to the PTP-MEG2, the protein conformations became unstable and the function of the pTyr recognition loop (Asn331-Cys338) would be disturbed. And thus, the ideal conformations needed for the catalytic activity was difficult to be maintained. In brief, these might be how the compound 1h worked. Furthermore, we also found that the key residues Arg332 would play a critical role in disturbing the residue interactions.