ethyl 2-amino-4-(benzo[d][1,3]dioxol-5-yl)thiophene-3-carboxylate | 849659-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: ethyl 2-amino-4-(benzo[d][1,3]dioxol-5-yl)thiophene-3-carboxylate
• 英文别名: 2-amino-4-benzo[1,3]dioxol-5-yl-thiophene-3-carboxylic acid ethyl ester；ethyl 2-amino-4-(1,3-benzodioxol-5-yl)thiophene-3-carboxylate
• CAS: 849659-34-3
• 化学式: C₁₄H₁₃NO₄S
• 分子量: 291.328
• InChiKey: WVUMZXGXSXTSDX-UHFFFAOYSA-N

物化性质

• 沸点：
  444.9±45.0 °C(Predicted)
• 密度：
  1.373±0.06 g/cm3(Predicted)

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：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  99
• 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-(benzo[d][1,3]dioxol-5-yl)thiophene-3-carboxylate 在 4-二甲氨基吡啶 、 水 、 potassium hydroxide 作用下， 以 吡啶 、 乙醇 为溶剂， 反应 8.17h， 生成 4-(2H-1,3-benzodioxol-5-yl)-2-{[(tert-butoxy)carbonyl]amino}thiophene-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2013.03.019
• 作为产物：
  描述：

  3,4-亚甲二氧苯乙酮 、 氰乙酸乙酯 在 吗啉 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 作用下， 以 乙醇 为溶剂， 反应 0.58h， 生成 ethyl 2-amino-4-(benzo[d][1,3]dioxol-5-yl)thiophene-3-carboxylate
  参考文献：
  名称：

  Novel 4-Oxothienopyrimidinyl Propanoic Acid Derivatives as AMPActivated Protein Kinase (AMPK) Activators

  摘要：

  腺苷5'-单磷酸(AMP)激活的蛋白激酶(AMPK)是一种高度保守的细胞能量感应器。AMPK已被确认为调节哺乳动物代谢功能的关键因子,并已成为治疗包括肥胖和2型糖尿病在内的代谢紊乱的理想靶点。本文描述了新型3-(4-氧代噻吩并[2,3-d]嘧啶-3(4H)-基)丙酸衍生物作为AMPK激活剂的合成和生物学评价。体内实验证明了本系列中的先导化合物具有降低血浆葡萄糖水平的原理验证作用。

  DOI：

  10.2174/1570180811666140122003044

文献信息

• [EN] THIENOPYRIMIDINE DERIVATIVES AS POTASSIUM CHANNEL INHIBITORS<br/>[FR] UTILISATION DE DERIVES DE LA THIENOPYRIMIDINE COMME INHIBITEURS DES CANAUX POTASSIQUES
  申请人：XENTION DISCOVERY LTD

  公开号：WO2004111057A1

  公开（公告）日：2004-12-23

  The present invention provides thienopyrimidine compounds which are potasium channels inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also provided.

  本发明提供了硫代嘧啶类化合物，它们是钾通道抑制剂。还提供了包含这些化合物的药物组合物，以及它们在治疗心律失常中的用途。
• Discovery and SAR development of thienopyridones: A class of small molecule AMPK activators
  作者：Gang Zhao、Rajesh R. Iyengar、Andrew S. Judd、Barbara Cool、William Chiou、Lemma Kifle、Ernst Frevert、Hing Sham、Philip R. Kym

  DOI：10.1016/j.bmcl.2007.04.011

  日期：2007.6

  AMP-activated protein kinase (AMPK) is well established as a sensor and regulator of intracellular and whole-body energy metabolism. A high-throughput screen was performed in order to identify chemotypes that are bound by AMPK. A novel thienopyridone compound (1) was identified and subsequently optimized. The structure-activity relationships that emerged from this effort are described. (c) 2007 Elsevier Ltd. All rights reserved.
• THIENOPYRIMIDINE DERIVATIVES AS POTASSIUM CHANNEL INHIBITORS
  申请人：Xention Limited

  公开号：EP1641803B1

  公开（公告）日：2009-03-18
• 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.
• US8889672B2
  申请人：——

  公开号：US8889672B2

  公开（公告）日：2014-11-18