Ethyl (2E,4Z)-5-bromo-5-(4-methylphenyl)-2,4-pentadienoate | 1002127-92-5

• 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-bromo-5-(4-methylphenyl)-2,4-pentadienoate
• 英文别名: ethyl (2E,4Z)-5-bromo-5-(4-methylphenyl)penta-2,4-dienoate
• CAS: 1002127-92-5
• 化学式: C₁₄H₁₅BrO₂
• 分子量: 295.176
• InChiKey: IPGACAOIVMWSRP-NPPGUXHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  Ethyl (2E,4Z)-5-bromo-5-(4-methylphenyl)-2,4-pentadienoate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三(2-呋喃基)膦 、 sodium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 9.0h， 生成 (2E,4Z)-5-(4-Ethoxyphenyl)-5-(4-methylphenyl)-2,4-pentadienoic acid
  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 、 sodium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 8.5h， 生成 Ethyl (2E,4Z)-5-bromo-5-(4-methylphenyl)-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.