(E)-3-(4-fluorophenyl)-3-[2-(piperidin-1-yl)-6-(trifluoromethyl)pyridine-3-yl]propenoic acid ethyl ester | 1002129-24-9

• 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: (E)-3-(4-fluorophenyl)-3-[2-(piperidin-1-yl)-6-(trifluoromethyl)pyridine-3-yl]propenoic acid ethyl ester
• 英文别名: (E)-3-(4-fluorophenyl)-3-[2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl]propenoic acid ethyl ester；(E)-3-(4-fluorophenyl)-3-[2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl]acrylic acid ethyl ester；ethyl (E)-3-(4-fluorophenyl)-3-[2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl]acrylate；ethyl (E)-3-(4-fluorophenyl)-3-[2-piperidin-1-yl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enoate
• CAS: 1002129-24-9
• 化学式: C₂₂H₂₂F₄N₂O₂
• 分子量: 422.422
• InChiKey: VDZUQNLNZWMGES-NBVRZTHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 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：

  (E)-3-(4-fluorophenyl)-3-[2-(piperidin-1-yl)-6-(trifluoromethyl)pyridine-3-yl]propenoic acid ethyl ester 在 manganese(IV) oxide 、 二异丁基氢化铝 、 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 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 (2E,4E)-5-(4-fluorophenyl)-N-(3-hydroxy-2-oxo-1,2,3,4-tetrahydro-5-quinolyl)-5-[2-(piperidin-1-yl)-6-trifluoromethylpyridin-3-yl]-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：

  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 (E)-3-(4-fluorophenyl)-3-[2-(piperidin-1-yl)-6-(trifluoromethyl)pyridine-3-yl]propenoic acid ethyl ester
  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.