ethyl 2-amino-4-(4'-nitrophenyl)thiophene-3-carboxylate

• 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 2-amino-4-(4'-nitrophenyl)thiophene-3-carboxylate
• 英文别名: ethyl 2-amino-4-(4-nitrophenyl)thiophene-3-carboxylate
• 化学式: C₁₃H₁₂N₂O₄S
• mdl: MFCD00298930
• 分子量: 292.315
• InChiKey: PZUSHWNNJRFJFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-amino-4-(4'-nitrophenyl)thiophene-3-carboxylate 在 盐酸 、 sodium methylate 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  3-甲基-5-苯基噻吩并[2,3-d]嘧啶-2,4（1H，3H）-二酮衍生物的合成和生物学评价用于治疗饮食性肥胖。

  摘要：

  甘油三酸酯是肝细胞中脂肪的主要部分和一半的脂质，在代谢中起着重要的作用，它是膳食脂肪的能量来源和转运体。在这项研究中，合成了33种基于3-甲基-5-苯基硫代[2,3-d]嘧啶-2,4（1H，3H）-二酮的衍生物，并评估了它们的降脂活性。其中，发现化合物1i在3T3-L1脂肪细胞中具有有效的降低甘油三酸酯的功效，与腺苷单磷酸激活的蛋白激酶（AMPK）激动剂Acadesine（AIACR）相当。此外，以50 mg kg（-1）d（-1）的剂量口服1i 5周可分别使平均体重和肝脏重量降低12.02％和32.00％，并调节血清甘油三酯水平。饮食诱导的肥胖小鼠。

  DOI：

  10.1248/cpb.c14-00258
• 作为产物：
  描述：

  2-Cyan-3-<4-nitro-phenyl>-but-2-en-saeure-aethylester 在 sulfur 、 三乙胺 作用下， 以41%的产率得到ethyl 2-amino-4-(4'-nitrophenyl)thiophene-3-carboxylate
  参考文献：
  名称：

  第1部分：衍生自乙基2-氨基-4-（4'-取代苯基）噻吩的一些新型单偶氮染料的合成和可见吸收光谱

  摘要：

  制备并表征了一些2-氨基-4-（4'-取代苯基）噻吩的单偶氮染料系列。物质的结构通过FT-IR，1 H NMR和质谱技术确认。研究了染料的结构，它们的吸收特性以及染料的溶剂变色和卤致变色行为之间的关系。将电子接受性取代基引入重氮部分会导致所有使用的溶剂发生大的红移。染料表现出正的溶剂变色作用，并讨论了与互变异构有关的溶剂变色性质。

  DOI：

  10.1016/j.saa.2014.04.042

文献信息

• Synthesis and structure–activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors
  作者：Paul M. Titchenell、H.D. Hollis Showalter、Jean-François Pons、Alistair J. Barber、Yafei Jin、David A. Antonetti

  DOI：10.1016/j.bmcl.2013.03.019

  日期：2013.5

  Recent evidence suggests atypical protein kinase C (aPKC) isoforms are required for both TNF- and VEGF-induced breakdown of the blood-retinal barrier (BRB) and endothelial permeability to 70 kDa dextran or albumin. A chemical library screen revealed a series of novel small molecule phenylthiophene based inhibitors of aPKC isoforms that effectively block permeability in cell culture and in vivo. In an effort to further elucidate the structural requirements of this series of inhibitors, we detail in this study a structure-activity relationship (SAR) built on screening hit 1, which expands on our initial pharmacophore model. The biological activity of our analogues was evaluated in models of bona fide aPKC-dependent signaling including NF kappa B driven-gene transcription as a marker for an inflammatory response and VEGF/TNF-induced vascular endothelial permeability. The EC50 for the most efficacious inhibitors (6, 32) was in the low nanomolar range in these two cellular assays. Our study demonstrates the key structural elements that confer inhibitory activity and highlights the requirement for electron-donating moieties off the C-4 aryl moiety of the 2-amino-3-carboxy-4-phenylthiophene backbone. These studies suggest that this class has potential for further development into small molecule aPKC inhibitors with therapeutic efficacy in a host of diseases involving increased vascular permeability and inflammation. (C) 2013 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：WO2005033102A3

  公开（公告）日：2005-07-28
• KOEBEL R. F.; NEEDHAM L. L.; BLANTON JR. C. D., J. MED. CHEM. <JMCM-AR>, 1975, 18, NO 2, 192-194
  作者：KOEBEL R. F.、 NEEDHAM L. L.、 BLANTON JR. C. D.

  DOI：——

  日期：——
• Compounds, Formulations, and Methods of Protein Kinase C Inhibition
  申请人：Antonetti David A.

  公开号：US20120302561A1

  公开（公告）日：2012-11-29

  The invention provides a method of inhibiting atypical protein kinase C (aPKC) comprising contacting an aPKC with a compound having a structure selected from the group consisting of structural formulas (I) to (IX). The invention further provides a method of inhibiting or reducing vascular permeability. The method comprising administering to a subject a composition comprising an amount of a compound having a structure selected from the group consisting of structural formulas (I) to (IX) effective to inhibit or reduce vascular permeability. A method of treating or preventing a disease or disorder characterized by abnormal vascular permeability, a method of inhibiting angiogenesis, a method of inhibiting cancer cell proliferation, a formulation, and a method of preparing a formulation also are provided.
• US4180503A
  申请人：——

  公开号：US4180503A

  公开（公告）日：1979-12-25