methyl (2E)-3-(4-ethynylphenyl)prop-2-enoate | 1420837-04-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl (2E)-3-(4-ethynylphenyl)prop-2-enoate
• 英文别名: methyl (E)-3-(4-ethynylphenyl)prop-2-enoate
• CAS: 1420837-04-2
• 化学式: C₁₂H₁₀O₂
• 分子量: 186.21
• InChiKey: GSIMHHRRGJELAA-CMDGGOBGSA-N

物化性质

• 沸点：
  295.5±23.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl (2E)-3-(4-ethynylphenyl)prop-2-enoate 在 copper(l) iodide 、 sodium tetrachloropalladate(II) 、 lithium hydroxide monohydrate 、 四甲基乙二胺 、 水 、 2-二叔丁基膦-1-苯基吲哚 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (E)-3-[4-[2-(2-methylphenyl)ethynyl]phenyl]prop-2-enoic acid
  参考文献：
  名称：

  Discovery of a Potent and Selective Free Fatty Acid Receptor 1 Agonist with Low Lipophilicity and High Oral Bioavailability

  摘要：

  The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.

  DOI：

  10.1021/jm301470a
• 作为产物：
  描述：

  3-(4-溴苯基)-2-丙酸甲酯 在 copper(l) iodide 、 sodium tetrachloropalladate(II) 、 四甲基乙二胺 、 potassium carbonate 、 2-二叔丁基膦-1-苯基吲哚 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 methyl (2E)-3-(4-ethynylphenyl)prop-2-enoate
  参考文献：
  名称：

  Discovery of a Potent and Selective Free Fatty Acid Receptor 1 Agonist with Low Lipophilicity and High Oral Bioavailability

  摘要：

  The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.

  DOI：

  10.1021/jm301470a

文献信息

• Niacin receptor agonists, compositions containing such compounds and methods of treatment
  申请人：Raghavan Subharekha

  公开号：US20060293364A1

  公开（公告）日：2006-12-28

  The present invention encompasses compounds of Formula I: as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating atherosclerosis, dyslipidemias and the like. Pharmaceutical compositions and methods of use are also included.

  本发明涵盖了Formula I的化合物： 以及其药用可接受的盐和水合物，用于治疗动脉粥样硬化、血脂异常等疾病。药物组合物和使用方法也包括在内。
• Cellular localisation of structurally diverse diphenylacetylene fluorophores
  作者：David R. Chisholm、Joshua G. Hughes、Thomas S. Blacker、Rachel Humann、Candace Adams、Daniel Callaghan、Alba Pujol、Nicola K. Lembicz、Angus J. Bain、John M. Girkin、Carrie A. Ambler、Andrew Whiting

  DOI：10.1039/d0ob01153c

  日期：——

  anticipate the effect that changing chemical structure can have on cellular localisation and fluorescence behaviour. To provide further chemical rationale for probe design, a series of donor–acceptor diphenylacetylene fluorophores with varying lipophilicities and structures were synthesised and analysed in human epidermal cells using a range of cellular imaging techniques. These experiments showed that, within

  荧光探针越来越多地用作各种生物物理实验中的报告分子，但在设计新化合物时，通常很难预测化学结构变化对细胞定位和荧光行为的影响。为了为探针设计提供进一步的化学原理，使用一系列细胞成像技术在人表皮细胞中合成和分析了一系列具有不同亲脂性和结构的供体-受体二苯乙炔荧光团。这些实验表明，在这个家族中，细胞定位的最大决定因素是整体亲脂性和可电离基团的存在。事实上，具有高 log  D的化合物发现值（> 5）定位于脂滴中，但它们的酯受体基团转化为相应的羧酸导致内质网定位的明显转变。具有强碱性胺基的轻度亲脂性化合物（log  D = 2-3）被证明仅限于溶酶体，即酸性细胞区室，但将这种带正电荷的基序作为酰胺隔离会导致细胞质和膜定位发生显着变化。最后，包括线粒体在内的特定细胞器可以通过结合诸如三苯基鏻部分的基团来靶向。总而言之，该说明说明了一系列指导原则，这些原则可以为其他荧光分子的设计提供信息，而且还表明，
• [EN] SYNTHETIC RETINOIDS (IN CELL MODULATION)<br/>[FR] RÉTINOÏDES SYNTHÉTIQUES (DANS LA MODULATION CELLULAIRE )
  申请人：UNIV DURHAM

  公开号：WO2018029473A1

  公开（公告）日：2018-02-15

  There are described novel compounds of formula I: (I) in which, in which A1, A2, A3, A4, R1 and R2 are each as herein defined, for use in the treatment or alleviation of an RAR mediated condition; and methods related thereto.

  已描述了公式I的新化合物：（I），其中A1、A2、A3、A4、R1和R2各自如本文所定义，用于治疗或缓解RAR介导的疾病；以及相关方法。
• Photoactivated cell-killing involving a low molecular weight, donor–acceptor diphenylacetylene
  作者：David R. Chisholm、Rebecca Lamb、Tommy Pallett、Valerie Affleck、Claire Holden、Joanne Marrison、Peter O'Toole、Peter D. Ashton、Katherine Newling、Andreas Steffen、Amanda K. Nelson、Christoph Mahler、Roy Valentine、Thomas S. Blacker、Angus J. Bain、John Girkin、Todd B. Marder、Andrew Whiting、Carrie A. Ambler

  DOI：10.1039/c9sc00199a

  日期：——

  including the destruction of diseased tissues and tumours. A novel class of photosensitiser, exemplified by DC324, has been designed possessing a modular, low molecular weight and ‘drug-like’ structure which is bioavailable and can be photoactivated by UV-A/405 nm or corresponding two-photon absorption of near-IR (800 nm) light, resulting in powerful cytotoxic activity, ostensibly through the production

  光敏剂的光活化可用于引发 ROS 的产生，用于潜在的治疗应用，包括破坏病变组织和肿瘤。以DC324为代表的新型光敏剂被设计成具有模块化、低分子量和“类药物”结构，具有生物可利用性，可通过 UV-A/405 nm 或相应的近光双光子吸收光活化。 IR (800 nm) 光，导致强大的细胞毒活性，表面上是通过在细胞环境中产生 ROS。多种体外细胞试验证实了 ROS 的形成，而体内细胞毒活性通过以下方式举例说明辐照和随后有针对性地破坏斑马鱼胚胎的特定区域。
• Niacin Receptor Agonists, Compositions Containing Such Compounds and Methods of Treatment
  申请人：Raghavan Subharekha

  公开号：US20120178750A1

  公开（公告）日：2012-07-12

  The present invention encompasses compounds of Formula I: as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating atherosclerosis, dyslipidemias and the like. Pharmaceutical compositions and methods of use are also included.

  本发明涵盖了I式化合物：以及其药学上可接受的盐和水合物，用于治疗动脉硬化、血脂异常等。还包括制药组合物和使用方法。