ethyl (2E,4Z)-5-[4-(oxetan-3-yloxy)phenyl]-5-(4-trifluoromethylphenyl)-2,4-pentadienoate | 1369534-98-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (2E,4Z)-5-[4-(oxetan-3-yloxy)phenyl]-5-(4-trifluoromethylphenyl)-2,4-pentadienoate
• 英文别名: ethyl (2E,4Z)-5-[4-(oxetan-3-yloxy)phenyl]-5-[4-(trifluoromethyl)phenyl]penta-2,4-dienoate
• CAS: 1369534-98-4
• 化学式: C₂₃H₂₁F₃O₄
• 分子量: 418.413
• InChiKey: UVCMGAYFKKAAGH-MSEFVAQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl (2E,4Z)-5-[4-(oxetan-3-yloxy)phenyl]-5-(4-trifluoromethylphenyl)-2,4-pentadienoate 在 水 、 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 (2E,4Z)-N-(3-hydroxy-2-oxo-1,2,3,4-tetrahydro-5-quinolyl)-5-[4-(oxetan-3-yloxy)phenyl]-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 四(三苯基膦)钯 、 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 potassium acetate 、 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 19.0h， 生成 ethyl (2E,4Z)-5-[4-(oxetan-3-yloxy)phenyl]-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