ethyl 4,5-diphenylthiophene-2-carboxylate | 19282-43-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: ethyl 4,5-diphenylthiophene-2-carboxylate
• 英文别名: 4,5-diphenyl-thiophene-2-carboxylic acid ethyl ester
• CAS: 19282-43-0
• 化学式: C₁₉H₁₆O₂S
• 分子量: 308.401
• InChiKey: HLSBISFVXMCFBQ-UHFFFAOYSA-N

物化性质

• 熔点：
  77.5 °C
• 沸点：
  415.3±45.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4,5-diphenylthiophene-2-carboxylate 在 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex 、 potassium carbonate 、 sodium hydroxide 、 palladium dichloride 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 为溶剂， 反应 4.0h， 生成 triphenyl-thiophene-2-carboxylic acid
  参考文献：
  名称：

  具有逐步、酯控制的区域选择性的四芳基噻吩的程序合成

  摘要：

  在此，我们报告了一种模块化合成路线，以通过酯活化/导向基团提供的程序化化学控制来获得具有四种不同取代基的四芳基化噻吩化合物。该方法能够通过区域选择性卤化和交叉偶联反应顺序地对噻吩的各个位置进行功能化。所描述的反应顺序以比以前的路线更高的产率提供了四芳基噻吩，并采用了实用的反应方案、简单的催化系统和较短的反应时间。

  DOI：

  10.1021/acs.orglett.1c02447
• 作为产物：
  描述：

  5-苯基-2-噻吩羧酸乙酯 在 溴 、 potassium carbonate 、 溶剂黄146 、 palladium dichloride 、 zinc(II) chloride 作用下， 以 乙醇 、 水 为溶剂， 反应 1.5h， 生成 ethyl 4,5-diphenylthiophene-2-carboxylate
  参考文献：
  名称：

  具有逐步、酯控制的区域选择性的四芳基噻吩的程序合成

  摘要：

  在此，我们报告了一种模块化合成路线，以通过酯活化/导向基团提供的程序化化学控制来获得具有四种不同取代基的四芳基化噻吩化合物。该方法能够通过区域选择性卤化和交叉偶联反应顺序地对噻吩的各个位置进行功能化。所描述的反应顺序以比以前的路线更高的产率提供了四芳基噻吩，并采用了实用的反应方案、简单的催化系统和较短的反应时间。

  DOI：

  10.1021/acs.orglett.1c02447

文献信息

• Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer
  作者：Goknil Pelin Coskun、Yagmur Ozhan、Vladimir Dobričić、Jelena Bošković、Rengin Reis、Hande Sipahi、Zafer Sahin、Seref Demirayak

  DOI：10.3390/pharmaceutics15051441

  日期：——

  Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds 7a, 7d, and 7f were promising. Among these, 7f (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds 7a, 7d and 7f were also tested for their cytotoxic effects on healthy cell line but only compound 7d showed selectivity. Compounds 7a, 7d, and 7f showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC50 value was observed for 7c (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds 7a (3.78 µM), 7c (2.60 µM), 7e (3.3 µM), and 7f (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds 7c, 7e, and 7f to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, 7a and 7f were identified as the most promising compounds.

  癌症是死亡率最高的疾病。药物研究有助于找到有希望的治疗方法，但目前迫切需要有选择性的候选药物。胰腺癌难以治疗，而且进展迅速。遗憾的是，目前的治疗方法效果不佳。本研究合成了十种新的二芳基噻吩-2-甲酰肼衍生物，并对其药理活性进行了评估。二维和三维抗癌活性研究表明，化合物 7a、7d 和 7f 具有良好的抗癌前景。其中，7f（4.86 µM）对 PaCa-2 细胞的二维抑制活性最佳。还测试了化合物 7a、7d 和 7f 对健康细胞系的细胞毒性作用，但只有化合物 7d 显示出选择性。根据球形直径，化合物 7a、7d 和 7f 对三维细胞系的抑制效果最好。对化合物的 COX-2 和 5-LOX 抑制活性进行了筛选。对于 COX-2，7c 的 IC50 值（10.13 µM）最佳，与标准值相比，所有化合物的抑制作用都明显降低。在 5-LOX 抑制研究中，与标准化合物相比，化合物 7a（3.78 µM）、7c（2.60 µM）、7e（3.3 µM）和 7f（2.94 µM）显示出有影响力的活性。在分子对接研究方面，化合物 7c、7e 和 7f 与 5-LOX 酶的结合模式为非氧化还原型或氧化还原型，而不是铁结合型。作为 5-LOX 和胰腺癌细胞系的双重抑制剂，7a 和 7f 被认为是最有前途的化合物。
• PROCESS FOR THE PREPARATION OF HETEROCYCLIC PENTALENE DERIVATIVES
  申请人：Basell Polyolefine GmbH

  公开号：EP1412347A1

  公开（公告）日：2004-04-28
• Process for the preparation of heterocyclic pentalene derivatives
  申请人：——

  公开号：US20040192931A1

  公开（公告）日：2004-09-30

  A process for preparing heterocyclic pentalene derivative having formula (I): wherein w is a sulfur atom (S), an oxygen atom (O) or a NR or PR group, wherein R is an hydrocarbon group; R 1 , R 2 , R 3 , and R 4 , equal to or different from each other, are hydrogen atoms or hydrocarbon groups; said process comprising the following steps: a) contacting a compound of formula (II) T is a OR, NR 2 , CCI 3 , CF 3 , Cl, Br, I, imidazolil or pirazolyl radical; with at least one molar equivalent of a vinyl compound of formula (III): wherein M is MgHal, Li, K, ZnHal, wherein Hal is chlorine, bromine or iodine; (II), (III) b) treating the compound of formula obtained in step a) with a Bronsted acid; c) treating the compound obtained in step b) with a reducing agent; and d) dehydrating the alcohol obtained in step c) in order to obtain the compound of formula (I).
• US6930190B2
  申请人：——

  公开号：US6930190B2

  公开（公告）日：2005-08-16
• [EN] PROCESS FOR THE PREPARATION OF HETEROCYCLIC PENTALENE DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DE DERIVES HETEROCYCLIQUES DE PENTALENE
  申请人：BASELL POLYOLEFINE GMBH

  公开号：WO2003014107A1

  公开（公告）日：2003-02-20

  A process for preparing heterocyclic pentalene derivative having formula (I): wherein w is a sulfur atom (S), an oxygen atom (O) or a NR or PR group, wherein R is an hydrocarbon group; R?1, R2, R3, and R4¿, equal to or different from each other, are hydrogen atoms or hydrocarbon groups; said process comprising the following steps: a) contacting a compound of formula (II) T is a OR, NR¿2?, CCI3, CF3, C1, Br, I, imidazolil or pirazolyl radical; with at least one molar equivalent of a vinyl compound of formula (III): wherein M is MgHal, Li, K, ZnHal, wherein Hal is chlorine, bromine or iodine; (II), (III) b) treating the compound of formula obtained in step a) with a Bronsted acid; c) treating the compound obtained in step b) with a reducing agent; and d) dehydrating the alcohol obtained in step c) in order to obtain the compound of formula (I).