ethyl 2-amino-4-(3-cyanophenyl)thiophene-3-carboxylate | 849659-40-1

• 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 2-amino-4-(3-cyanophenyl)thiophene-3-carboxylate
• CAS: 849659-40-1
• 化学式: C₁₄H₁₂N₂O₂S
• 分子量: 272.327
• InChiKey: ICVSYDFPWXCRSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-amino-4-(3-cyanophenyl)thiophene-3-carboxylate 在 四氯化锡 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 生成 N-(5-benzoyl-4-(3-cyanophenyl)thiophen-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide
  参考文献：
  名称：

  Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors

  摘要：

  Novel series of N-(5-(arylcarbonyl) thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl) amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (ROR gamma t) inhibitors. SAR studies of the ROR gamma t HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.021
• 作为产物：
  描述：

  3-乙酰苯腈 、 氰乙酸乙酯 在 吗啉 、 sulfur 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 以52%的产率得到ethyl 2-amino-4-(3-cyanophenyl)thiophene-3-carboxylate
  参考文献：
  名称：

  芳基烷基酮在 2-氨基噻吩的一锅 Gewald 合成中

  摘要：

  通过芳基烷基酮与氰基乙酸乙酯和元素硫在乙酸吗啉和过量吗啉存在下的一锅 Gewald 反应，在 4-位带有各种芳基的 2-氨基噻吩-3-羧酸盐很容易以良好到中等的产率获得.

  DOI：

  10.1055/s-2006-951484

文献信息

• Aryl Alkyl Ketones in a One-Pot Gewald Synthesis of 2-Aminothiophenes
  作者：Victor Tormyshev、Anthony Flinn、Dmitry Trukhin、Olga Rogozhnikova、Tatiana Mikhalina、Tatiana Troitskaya

  DOI：10.1055/s-2006-951484

  日期：2006.9

  2-Aminothiophene-3-carboxylates bearing various aryl groups at the 4-position are readily obtained in good to moderate yields by the one-pot Gewald reaction of aryl alkyl ketones with ethyl cyanoacetate and elemental sulfur in the presence of morpholinium acetate and excess morpholine.

  通过芳基烷基酮与氰基乙酸乙酯和元素硫在乙酸吗啉和过量吗啉存在下的一锅 Gewald 反应，在 4-位带有各种芳基的 2-氨基噻吩-3-羧酸盐很容易以良好到中等的产率获得.
• 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
• 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.
• US7915267B2
  申请人：——

  公开号：US7915267B2

  公开（公告）日：2011-03-29
• Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors
  作者：Yonghui Wang、Wei Cai、Guifeng Zhang、Ting Yang、Qian Liu、Yaobang Cheng、Ling Zhou、Yingli Ma、Ziqiang Cheng、Sijie Lu、Yong-Gang Zhao、Wei Zhang、Zhijun Xiang、Shuai Wang、Liuqing Yang、Qianqian Wu、Lisa A. Orband-Miller、Yan Xu、Jing Zhang、Ruina Gao、Melanie Huxdorf、Jia-Ning Xiang、Zhong Zhong、John D. Elliott、Stewart Leung、Xichen Lin

  DOI：10.1016/j.bmc.2013.12.021

  日期：2014.1

  Novel series of N-(5-(arylcarbonyl) thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl) amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (ROR gamma t) inhibitors. SAR studies of the ROR gamma t HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration. (C) 2013 Elsevier Ltd. All rights reserved.