2-Amino-4-(3-methylphenyl)-thiophene-3-carboxylic acid ethyl ester | 255713-71-4

• 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: 2-Amino-4-(3-methylphenyl)-thiophene-3-carboxylic acid ethyl ester
• 英文别名: 2-amino-3-carboethoxy-4-(3-methylphenyl)thiophene；ethyl 2-amino-4-(3-methylphenyl)thiophene-3-carboxylate
• CAS: 255713-71-4
• 化学式: C₁₄H₁₅NO₂S
• 分子量: 261.345
• InChiKey: RLFQMSHKFIHAAE-UHFFFAOYSA-N

物化性质

• 沸点：
  396.6±42.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  2-Amino-4-(3-methylphenyl)-thiophene-3-carboxylic acid ethyl ester 在 4-二甲氨基吡啶 、 水 、 N,N'-羰基二咪唑 、 potassium hydroxide 作用下， 以 吡啶 、 乙醇 、 二氯甲烷 为溶剂， 反应 26.17h， 生成 benzyl 2-{[(tert-butoxy)carbonyl]amino}-4-(3-methylphenyl)thiophene-3-carboxylate
  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：

  氰乙酸乙酯 、 3'-甲基苯乙酮 在 ammonium acetate 、 溶剂黄146 、 sulfur 、 二乙胺 作用下， 以 甲苯 、 乙醇 为溶剂， 反应 3.0h， 以62%的产率得到2-Amino-4-(3-methylphenyl)-thiophene-3-carboxylic acid ethyl ester
  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

文献信息

• Piperazinyl pyrimidine dione compounds selective for adrenoceptors
  申请人：Abbott Laboratories

  公开号：US06166019A1

  公开（公告）日：2000-12-26

  Compounds of Formula I and II and their pharmaceutically acceptable, salts, esters and prodrugs thereof are selective alpha-1D adrenoceptor anatagonists and may be useful for treating disease states.

  公式I和II的化合物及其药用可接受的盐、酯及其前药是选择性α-1D肾上腺素受体拮抗剂，可能对治疗疾病状态有用。
• Pharmaceutically active compounds and methods of use
  申请人：——

  公开号：US20030073733A1

  公开（公告）日：2003-04-17

  New fused thiophene compounds are provided and methods of using those compounds for a variety of therapeutic indications. Compounds of the invention are particularly useful for treatment of neuropathic pain.

  提供了新的融合噻吩化合物，并提供了使用这些化合物治疗各种治疗适应症的方法。该发明的化合物特别适用于治疗神经病性疼痛。
• NOVEL COMPOUNDS
  申请人：Chen Deborah

  公开号：US20120252805A1

  公开（公告）日：2012-10-04

  The present invention relates to novel NADPH oxidase II inhibitors and their use in the treatment of diseases mediated by the NADPH oxidase II enzyme.

  本发明涉及新型NADPH氧化酶II抑制剂及其在治疗由NADPH氧化酶II酶介导的疾病中的应用。
• HETEROCYCLIC AMIDE COMPOUND AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1953148B1

  公开（公告）日：2012-02-29
• Two Novel and Potent 3-[(o-Methoxyphenyl)piperazinylethyl]-5-phenylthieno[2,3-d]pyrimidine-2,4-diones Selective for the α1D Receptor
  作者：William A Carroll、Kevin B Sippy、Timothy A Esbenshade、Steven A Buckner、Arthur A Hancock、Michael D Meyer

  DOI：10.1016/s0960-894x(01)00159-7

  日期：2001.5

  ,The synthesis and in vitro characterization of A-119637 and A-123189, two novel, selective and potent alpha (1D) antagonists, are described. (C) 2001 Elsevier Science Ltd. All rights reserved.