Ethyl 2-amino-4-(2-naphthyl)thiophene-3-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: Ethyl 2-amino-4-(2-naphthyl)thiophene-3-carboxylate
• 英文别名: ethyl 2-amino-4-naphthalen-2-ylthiophene-3-carboxylate
• 化学式: C₁₇H₁₅NO₂S
• mdl: MFCD01922935
• 分子量: 297.378
• InChiKey: YIRKGFGMQSGTEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 2-amino-4-(2-naphthyl)thiophene-3-carboxylate 在 potassium carbonate 作用下， 以 丙酮 、 正丁醇 为溶剂， 反应 61.5h， 生成 N'-[(3,4-dihydroxyphenyl)methylene]-[4-oxo-5-(naphthalen-2-yl)-thieno[2,3-d]pyrimidin-3(4H)-yl]acetohydrazone
  参考文献：
  名称：

  Synthesis and anti-tumor activities of N′-benzylidene-2-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazone derivatives

  摘要：

  A compound with a cyclic thienopyrimidine moiety and an aceto-hydrazone moiety in its chemical structure was discovered in a cell-based screening to have noticeable cytotoxicity on several tumor cell lines. A total of 38 derivatives of this compound were synthesized at five steps with high yields. These compounds were tested in standard MTT assays, and several compounds exhibited improved cytotoxic activities. The most potent compounds have IC50 values of 10-20 mu M on A549, HeLa, and MBA-MD-231 tumor cells. Flow cytometry analysis of several active compounds and subsequent examination of caspase activation indicate that they induce caspase-dependent apoptosis in tumor cells. In addition, these compounds do not have obvious effect on a normal cell line HEK-293T, demonstrating the desired selectivity against tumor cells. Results from a fluorescence polarization-based in vitro binding assay indicate that this class of compounds does not significantly interrupt the interactions between Mcl-1 and Bid. Their cytotoxicity is achieved presumably through other mechanisms. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.061
• 作为产物：
  描述：

  氰乙酸乙酯 、 2-萘乙酮 在 吗啉 、 aluminum oxide 、 sulfur 作用下， 反应 0.25h， 生成 Ethyl 2-amino-4-(2-naphthyl)thiophene-3-carboxylate
  参考文献：
  名称：

  Synthesis and anti-tumor activities of N′-benzylidene-2-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazone derivatives

  摘要：

  A compound with a cyclic thienopyrimidine moiety and an aceto-hydrazone moiety in its chemical structure was discovered in a cell-based screening to have noticeable cytotoxicity on several tumor cell lines. A total of 38 derivatives of this compound were synthesized at five steps with high yields. These compounds were tested in standard MTT assays, and several compounds exhibited improved cytotoxic activities. The most potent compounds have IC50 values of 10-20 mu M on A549, HeLa, and MBA-MD-231 tumor cells. Flow cytometry analysis of several active compounds and subsequent examination of caspase activation indicate that they induce caspase-dependent apoptosis in tumor cells. In addition, these compounds do not have obvious effect on a normal cell line HEK-293T, demonstrating the desired selectivity against tumor cells. Results from a fluorescence polarization-based in vitro binding assay indicate that this class of compounds does not significantly interrupt the interactions between Mcl-1 and Bid. Their cytotoxicity is achieved presumably through other mechanisms. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.061

文献信息

• Facile approach to the synthesis of substituted thieno[2,3-<i>d</i>]pyrimidin-4-ones
  作者：Anna Hovhannisyan、Lilit Aristakesyan、Gagik Melikyan

  DOI：10.1515/hc-2012-0095

  日期：2012.12.1

  Abstract Condensation of Gewald’s thiophenes substituted with a dimethylaminomethyleneamino group at position 2 with primary amines yields 5/6-aryl-thieno[2,3-d]pyrimidin-4-ones with variable substituents at the N3 position.

  摘要 Gewald's 噻吩在 2 位被二甲基氨基亚甲基氨基取代，与伯胺缩合生成 5/6-芳基-噻吩并[2,3-d]嘧啶-4-酮，在 N3 位具有可变取代基。
• Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity
  作者：Deju Ye、Yu Zhang、Fei Wang、Mingfang Zheng、Xu Zhang、Xiaomin Luo、Xu Shen、Hualiang Jiang、Hong Liu

  DOI：10.1016/j.bmc.2010.01.055

  日期：2010.3

  A series of novel thiophene derivatives was designed, synthesized and their activities as competitive inhibitors of protein tyrosine phosphatase (PTPs) 1B (PTP1B) inhibitors were evaluated. All the compounds showed inhibitory potencies, and 10 of these exhibited moderate inhibitory activities with IC50 values less than 10 mu M. The activity of the most potent compound P28 (IC50 = 2.1 mu M) was 15 times higher than that of the hit compound P01. Further, four representative compounds (P19, P22, P28, and P31) demonstrated remarkably high selectivities against other PTPs (e. g., PTP alpha, LAR, CD45, and TCPTP); P19 exhibited greater than sixfold selectivity over highly homologous TCPTP. More importantly, these compounds are permeable to cell membranes. The treatment of CHO-K1 cells with P28 (10 mu M) resulted in increased phosphorylation of AKT, which suggested extensive cellular activity of this compound. The novel chemical entities reported in this study could be used for overcoming the poor selectivity and low cellular activity of PTP1B inhibitors and might represent a starting point for development of therapeutic PTP inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.
• [EN] THIOPHENE-BASED COMPOUNDS EXHIBITING ATP-UTILIZING ENZYME INHIBITORY ACTIVITY, AND COMPOSITIONS, AND USES THEREOF<br/>[FR] COMPOSES A BASE DE THIOPHENE PRESENTANT UNE ACTIVITE D'INHIBITION D'ENZYMES UTILISANT L'ATP, COMPOSITIONS CONTENANT CES COMPOSES ET UTILISATIONS
  申请人：AMPHORA DISCOVERY CORP

  公开号：WO2005033102A2

  公开（公告）日：2005-04-14

  Thiophene-based compounds of formula (I) exhibiting ATP-utilizing enzyme inhibitory activity, methods of using compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions comprising compounds exhibiting ATP-utilizing enzyme inhibitory activity, are disclosed. These compounds are useful in the treatment of Alzheimer’s disease, stroke, diabetes, obesity, inflammation and cancer.
• Synthesis and anti-tumor activities of N′-benzylidene-2-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazone derivatives
  作者：Jiangping Lou、Zhen Liu、Yan Li、Mi Zhou、Zhengxi Zhang、Shu Zheng、Renxiao Wang、Jian Li

  DOI：10.1016/j.bmcl.2011.09.061

  日期：2011.11

  A compound with a cyclic thienopyrimidine moiety and an aceto-hydrazone moiety in its chemical structure was discovered in a cell-based screening to have noticeable cytotoxicity on several tumor cell lines. A total of 38 derivatives of this compound were synthesized at five steps with high yields. These compounds were tested in standard MTT assays, and several compounds exhibited improved cytotoxic activities. The most potent compounds have IC50 values of 10-20 mu M on A549, HeLa, and MBA-MD-231 tumor cells. Flow cytometry analysis of several active compounds and subsequent examination of caspase activation indicate that they induce caspase-dependent apoptosis in tumor cells. In addition, these compounds do not have obvious effect on a normal cell line HEK-293T, demonstrating the desired selectivity against tumor cells. Results from a fluorescence polarization-based in vitro binding assay indicate that this class of compounds does not significantly interrupt the interactions between Mcl-1 and Bid. Their cytotoxicity is achieved presumably through other mechanisms. (C) 2011 Elsevier Ltd. All rights reserved.