ethyl (2E,4E)-5-(4-formylphenyl)-5-(4-trifluoromethylphenyl)-2,4-pentadienoate | 1369534-89-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ethyl (2E,4E)-5-(4-formylphenyl)-5-(4-trifluoromethylphenyl)-2,4-pentadienoate
• 英文别名: ethyl (2E,4E)-5-(4-formylphenyl)-5-[4-(trifluoromethyl)phenyl]penta-2,4-dienoate
• CAS: 1369534-89-3
• 化学式: C₂₁H₁₇F₃O₃
• 分子量: 374.359
• InChiKey: ZYTRIZPMQOQULV-IHKVXXGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl (2E,4E)-5-(4-formylphenyl)-5-(4-trifluoromethylphenyl)-2,4-pentadienoate 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 (2E,4E)-5-(4-formylphenyl)-N-(isoquinolin-5-yl)-5-(4-trifluoromethylphenyl)-2,4-pentadienamide
  参考文献：
  名称：

  Discovery of Novel 5,5-Diarylpentadienamides as Orally Available Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists

  摘要：

  We have developed a novel and potent chemical series of 5,5-diphenylpentadienamides for targeting TRPV1 in vitro and in vivo. In this investigation, we examined a variety of replacements for the S-position of dienamides with the goal of addressing issues related to pharmacokinetics. Our data suggest that substitution with alkoxy groups on the phenyl ring at the S-position increases their ability to penetrate the blood brain barrier. This investigation culminated in the discovery of compound (R)-36b, which showed a good pharmacokinetic profile. In vivo, compound (R)-36b was found to be effective at reversing mechanical allodynia in rats in a dose-dependent manner, and it reversed thermal hyperalgesia in a model of neuropathic pain induced by sciatic nerve injury.

  DOI：

  10.1021/jm300101n
• 作为产物：
  描述：

  反式-4-氧基-2-丁烯酸乙酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 四(三苯基膦)钯 、 三(2-呋喃基)膦 、 sodium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 13.0h， 生成 ethyl (2E,4E)-5-(4-formylphenyl)-5-(4-trifluoromethylphenyl)-2,4-pentadienoate
  参考文献：
  名称：

  Discovery of Novel 5,5-Diarylpentadienamides as Orally Available Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists

  摘要：

  We have developed a novel and potent chemical series of 5,5-diphenylpentadienamides for targeting TRPV1 in vitro and in vivo. In this investigation, we examined a variety of replacements for the S-position of dienamides with the goal of addressing issues related to pharmacokinetics. Our data suggest that substitution with alkoxy groups on the phenyl ring at the S-position increases their ability to penetrate the blood brain barrier. This investigation culminated in the discovery of compound (R)-36b, which showed a good pharmacokinetic profile. In vivo, compound (R)-36b was found to be effective at reversing mechanical allodynia in rats in a dose-dependent manner, and it reversed thermal hyperalgesia in a model of neuropathic pain induced by sciatic nerve injury.

  DOI：

  10.1021/jm300101n

文献信息

• Discovery of Novel 5,5-Diarylpentadienamides as Orally Available Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists
  作者：Osamu Saku、Hiroshi Ishida、Eri Atsumi、Yoshiyuki Sugimoto、Hiroshi Kodaira、Yoshimitsu Kato、Shiro Shirakura、Yoshisuke Nakasato

  DOI：10.1021/jm300101n

  日期：2012.4.12

  We have developed a novel and potent chemical series of 5,5-diphenylpentadienamides for targeting TRPV1 in vitro and in vivo. In this investigation, we examined a variety of replacements for the S-position of dienamides with the goal of addressing issues related to pharmacokinetics. Our data suggest that substitution with alkoxy groups on the phenyl ring at the S-position increases their ability to penetrate the blood brain barrier. This investigation culminated in the discovery of compound (R)-36b, which showed a good pharmacokinetic profile. In vivo, compound (R)-36b was found to be effective at reversing mechanical allodynia in rats in a dose-dependent manner, and it reversed thermal hyperalgesia in a model of neuropathic pain induced by sciatic nerve injury.