ethyl (E)-3-(2-dimethylamino-6-trifluoromethylpyridin-3-yl)-3-(4-fluorophenyl)acrylate | 1369535-01-2

• 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: ethyl (E)-3-(2-dimethylamino-6-trifluoromethylpyridin-3-yl)-3-(4-fluorophenyl)acrylate
• 英文别名: ethyl (E)-3-[2-(dimethylamino)-6-(trifluoromethyl)pyridin-3-yl]-3-(4-fluorophenyl)prop-2-enoate
• CAS: 1369535-01-2
• 化学式: C₁₉H₁₈F₄N₂O₂
• 分子量: 382.358
• InChiKey: HYQZKIVLHIDUFA-RVDMUPIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl (E)-3-(2-dimethylamino-6-trifluoromethylpyridin-3-yl)-3-(4-fluorophenyl)acrylate 在 manganese(IV) oxide 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 37.5h， 生成 methyl (2E,4E)-5-(2-dimethylamino-6-trifluoromethylpyridin-3-yl)-5-(4-fluorophenyl)-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
• 作为产物：
  描述：

  2-氯-6-三氟甲基烟酸 在 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 188.0h， 生成 ethyl (E)-3-(2-dimethylamino-6-trifluoromethylpyridin-3-yl)-3-(4-fluorophenyl)acrylate
  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.