ethyl (2E)-3-(4-amino-2-fluorophenyl)prop-2-enoate | 865137-76-4

• 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: ethyl (2E)-3-(4-amino-2-fluorophenyl)prop-2-enoate
• 英文别名: ethyl 4-amino-2-fluorocinnamate；ethyl (2E)-3-(4-amino-2-fluorophenyl)acrylate；ethyl(2E)-3-(4-amino-2-fluorophenyl)acrylate；ethyl (E)-3-(4-amino-2-fluorophenyl)prop-2-enoate
• CAS: 865137-76-4
• 化学式: C₁₁H₁₂FNO₂
• 分子量: 209.22
• InChiKey: KCINNDBBSQBCEG-GQCTYLIASA-N

物化性质

• 沸点：
  347.5±32.0 °C(Predicted)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (2E)-3-(4-amino-2-fluorophenyl)prop-2-enoate 在 palladium 10% on activated carbon 、 水 、 氢气 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 为溶剂， 反应 70.0h， 生成 3-[4-({[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanoic acid
  参考文献：
  名称：

  Discovery of Phenylpropanoic Acid Derivatives Containing Polar Functionalities as Potent and Orally Bioavailable G Protein-Coupled Receptor 40 Agonists for the Treatment of Type 2 Diabetes

  摘要：

  As part of a program to identify potent GPR40 agonists with drug-like properties suitable for clinical development, the incorporation of polar substituents was explored with the intention of decreasing the lipophilicity of our recently disclosed phenylpropanoic acid derivative 1. This incorporation would allow us to mitigate the cytotoxicity issues observed with compound 1 and enable us to move away from the multifunctional free fatty acid-like structure. Substitutions on the 2',6'-dimethylbiphenyl ring were initially undertaken, which revealed the feasibility of introducing polar functionalities at the biphenyl 4'-position. Further optimization of this position and the linker led to the discovery of several 4'-alkoxybiphenyl derivatives, which showed potent GPR40 agonist activities with the best balance in terms of improved cytotoxicity profiles and favorable pharmacokinetic properties. Among them, 3-{2-fluoro-4[({4'-[(4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)amino]phenyl}propanoic acid (35) exhibited a robust plasma glucose-lowering effect and insulinotropic action during an oral glucose tolerance test in rats with impaired glucose tolerance.

  DOI：

  10.1021/jm2016123
• 作为产物：
  描述：

  4-溴-3-氟苯胺 、 丙烯酸乙酯 在 palladium diacetate N,N-二异丙基乙胺 、 三(邻甲基苯基)磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 ethyl (2E)-3-(4-amino-2-fluorophenyl)prop-2-enoate
  参考文献：
  名称：

  EP1726580

  摘要：

  公开号：

文献信息

• Aminophenylpropanoic Acid Derivative
  申请人：Yasuma Tsuneo

  公开号：US20080269220A1

  公开（公告）日：2008-10-30

  A compound represented by the formula (1): wherein each symbol is as defined in the specification, and a salt thereof and a prodrug thereof unexpectedly have superior GPR40 receptor agonist activity, superior in the properties as a pharmaceutical product such as stability and the like, and can be a safe and useful pharmaceutical agent as a drug for the prophylaxis or treatment of GPR40 receptor related pathology or diseases such as diabetes and the like.

  化合物的化学式为（1）：其中每个符号如规范所定义，其盐和前药意外地具有更优越的GPR40受体激动剂活性，在药品产品的稳定性等方面具有优越性，并且可以作为安全有效的药物用于预防或治疗GPR40受体相关的病理或疾病，例如糖尿病等。
• Cyclopropanecarboxylic acid compound
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US08153694B2

  公开（公告）日：2012-04-10

  A compound of the formula (I): wherein each symbol is as defined in the description, a salt thereof, and a prodrug thereof of the present invention unexpectedly have a superior GPR40 receptor agonist activity and superior properties as pharmaceutical products such as stability and the like, and can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor-related pathology or diseases in mammals.

  公式（I）的化合物：其中每个符号如描述中所定义，其盐和前药，意外地具有优越的GPR40受体激动剂活性和作为药物产品的优越性能，如稳定性等，并且可以是安全有效的药物剂型，用于哺乳动物的GPR40受体相关病理或疾病的预防或治疗。
• BIS(TRIMETHYLSILYL)PHENYL COMPOUND OR SALT THEREOF, AND USE THEREOF
  申请人：Suda Yoshimitsu

  公开号：US20100210591A1

  公开（公告）日：2010-08-19

  The present invention provides a compound that exhibits an excellent antitumor effect and reduces side effects, such as skin disorders, of the existing retinoid by selectively activating on the nuclear receptor RARα, thereby possibly producing significant improvement of clinical profits. Specifically, the present invention provides a bis(trimethylsilyl)phenyl compound represented by Formula (I): wherein X is N or CH; Y is O or S; R1, R2, and R3 are the same or different and are hydrogen or lower alkyl; R4 and R5 are the same or different and are hydrogen, lower alkyl, or halogen; and a bond between a carbon atom to which R1 is attached and a carbon atom to which R2 is attached is a single bond or a double bond; or a salt thereof.

  本发明提供了一种化合物，该化合物通过选择性激活核受体RARα，展现出优异的抗肿瘤效果并减少现有维甲酸类药物的副作用，如皮肤疾病，从而可能显著提高临床效益。具体而言，本发明提供了一种由式（I）表示的双（三甲基硅基）苯基化合物：其中X是N或CH；Y是O或S；R1、R2和R3相同或不同，是氢或低碳基；R4和R5相同或不同，是氢、低碳基或卤素；以及连接R1和R2所连接的碳原子之间的键是单键或双键；或其盐。
• Aminophenylpropanoic acid derivative
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07786165B2

  公开（公告）日：2010-08-31

  A compound represented by the formula (1): wherein each symbol is as defined in the specification, and a salt thereof and a prodrug thereof unexpectedly have superior GPR40 receptor agonist activity, superior in the properties as a pharmaceutical product such as stability and the like, and can be a safe and useful pharmaceutical agent as a drug for the prophylaxis or treatment of GPR40 receptor related pathology or diseases such as diabetes and the like.

  化合物的化学式为(1)：其中每个符号如规范中所定义，其盐和前药意外地具有优越的GPR40受体激动剂活性，具有制药产品的优越性能，例如稳定性等，并且可以作为治疗或预防GPR40受体相关病理或疾病，如糖尿病等的药物而成为安全有效的药物。
• Cyclopropanecarboxylic Acid Compound
  申请人：Yasuma Tsuneo

  公开号：US20100144806A1

  公开（公告）日：2010-06-10

  A compound of the formula (I): wherein each symbol is as defined in the description, a salt s thereof, and a prodrug thereof of the present invention unexpectedly have a superior GPR40 receptor agonist activity and superior properties as pharmaceutical products such as stability and the like, and can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor-related pathology or diseases in mammals.

  公式（I）的化合物：其中每个符号的定义如描述，其盐和其前药，本发明意外地具有优越的GPR40受体激动剂活性和作为药物产品的优越性能，例如稳定性等，可以作为安全和有用的药物剂量用于哺乳动物的预防或治疗GPR40受体相关病理或疾病。