ethyl (2E)-3-[6-trifluoromethyl-3-pyridinyl]-2-propenoate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (2E)-3-[6-trifluoromethyl-3-pyridinyl]-2-propenoate
• 英文别名: (E)-ethyl 3-(6-(trifluoromethyl)pyridin-3-yl)acrylate；(E)-ethyl 3-(6-trifluoromethylpyridin-3-yl)acrylate；(E)-ethyl-3-(6-(trifluoromethyl)pyridin-3-yl)acrylate；ethyl (E)-3-[6-(trifluoromethyl)pyridin-3-yl]prop-2-enoate
• 化学式: C₁₁H₁₀F₃NO₂
• 分子量: 245.201
• InChiKey: KNHCACXUZYKFRM-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl (2E)-3-[6-trifluoromethyl-3-pyridinyl]-2-propenoate 在 氢氧化钾 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 (2E)-3-[6-(三氟甲基)-3-吡啶基]丙烯酸
  参考文献：
  名称：

  Discovery of Potent, Orally Available Vanilloid Receptor-1 Antagonists. Structure−Activity Relationship of N-Aryl Cinnamides

  摘要：

  The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators: particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1): an antagonist that blocks the capsaicin-induced and pH-induced uptake of Ca-45(2+) in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 +/- 5 and 150 +/- 80 nM, respectively. In this report.. we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (F-oral = 39% and 17%. respectively).

  DOI：

  10.1021/jm049485i
• 作为产物：
  描述：

  磷酰基乙酸三乙酯 、 6-三氟甲基吡啶-3-醛 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 ethyl (2E)-3-[6-trifluoromethyl-3-pyridinyl]-2-propenoate
  参考文献：
  名称：

  Discovery of Potent, Orally Available Vanilloid Receptor-1 Antagonists. Structure−Activity Relationship of N-Aryl Cinnamides

  摘要：

  The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators: particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1): an antagonist that blocks the capsaicin-induced and pH-induced uptake of Ca-45(2+) in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 +/- 5 and 150 +/- 80 nM, respectively. In this report.. we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (F-oral = 39% and 17%. respectively).

  DOI：

  10.1021/jm049485i

文献信息

• Design, Synthesis, and Biological Evaluation of Potent and Selective Class IIa Histone Deacetylase (HDAC) Inhibitors as a Potential Therapy for Huntington’s Disease
  作者：Roland W. Bürli、Christopher A. Luckhurst、Omar Aziz、Kim L. Matthews、Dawn Yates、Kathy. A. Lyons、Maria Beconi、George McAllister、Perla Breccia、Andrew J. Stott、Stephen D. Penrose、Michael Wall、Marieke Lamers、Philip Leonard、Ilka Müller、Christine M. Richardson、Rebecca Jarvis、Liz Stones、Samantha Hughes、Grant Wishart、Alan F. Haughan、Catherine O’Connell、Tania Mead、Hannah McNeil、Julie Vann、John Mangette、Michel Maillard、Vahri Beaumont、Ignacio Munoz-Sanjuan、Celia Dominguez

  DOI：10.1021/jm4011884

  日期：2013.12.27

  Inhibition of class IIa histone deacetylase (HDAC) enzymes have been suggested as a therapeutic strategy for a number of diseases, including Huntington’s disease. Catalytic-site small molecule inhibitors of the class IIa HDAC4, -5, -7, and -9 were developed. These trisubstituted diarylcyclopropanehydroxamic acids were designed to exploit a lower pocket that is characteristic for the class IIa HDACs

  有人提出抑制IIa类组蛋白脱乙酰基酶（HDAC）酶可以作为许多疾病的治疗策略，包括亨廷顿氏病。开发了IIa类HDAC4，-5，-7和-9的催化位点小分子抑制剂。这些三取代的二芳基环丙烷异羟肟酸被设计用于开发IIa类HDAC特有的下部口袋，而其他HDAC类中不存在。所选的抑制剂与人HDAC4的催化结构域共结晶。我们以“闭环”形式描述了第一个HDAC4催化域晶体结构，在我们看来代表了生物学相关的构象。我们已经证明这些分子可以区分IIa类HDAC与I类和IIb类亚型。它们表现出药代动力学特性，应该能够评估它们在周围和中枢神经系统疾病中的治疗效果。这些选择性抑制剂提供了用于评估体内临床前模型中潜在功效的手段。
• [EN] HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS D'HISTONE DÉSACÉTYLASE, ET COMPOSITIONS ET PROCÉDÉS POUR LES UTILISER
  申请人：CHDI FOUNDATION INC

  公开号：WO2012103008A1

  公开（公告）日：2012-08-02

  Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.

  提供了某些Formula I的组蛋白去乙酰化酶（HDAC）抑制剂，以及它们的组合物和使用方法。
• NOVEL BRONCHODILATING ALPHA, BETA-UNSATURATED ISOQUINOLINE AMIDES
  申请人：Dalence Maria

  公开号：US20100256101A1

  公开（公告）日：2010-10-07

  The invention relates to novel compounds having the general formula (I), and which compounds are useful to manufacture a medicament to treat a disorder or disease characterized by bronchoconstriction, e.g. COPD and asthma, and vasoconstriction, e.g. hypertension.

  本发明涉及具有一般式(I)的新化合物，这些化合物可用于制造治疗支气管收缩（例如COPD和哮喘）和血管收缩（例如高血压）等疾病或疾病的药物。
• Bronchodilating alpha, beta-unsaturated isoquinoline amides
  申请人：Respiratorius AB

  公开号：US08318768B2

  公开（公告）日：2012-11-27

  The invention relates to novel compounds having the general formula (I), and which compounds are useful to manufacture a medicament to treat a disorder or disease characterized by bronchoconstriction, e.g. COPD and asthma, and vasoconstriction, e.g. hypertension.

  该发明涉及具有一般式（I）的新化合物，这些化合物可用于制造治疗支气管收缩（例如COPD和哮喘）和血管收缩（例如高血压）等疾病或疾病的药物。
• HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF
  申请人：Luckhurst Christopher A

  公开号：US20140163009A1

  公开（公告）日：2014-06-12

  Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.

  提供了某些式I的组蛋白去乙酰化酶（HDAC）抑制剂，它们的组成物以及使用它们的方法。