(2E,4E)-N-(isoquinolin-5-yl)-5-(4-trifluoromethylphenyl)-2,4-pentadienamide | 1369534-86-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (2E,4E)-N-(isoquinolin-5-yl)-5-(4-trifluoromethylphenyl)-2,4-pentadienamide
• 英文别名: (2E,4E)-N-isoquinolin-5-yl-5-[4-(trifluoromethyl)phenyl]penta-2,4-dienamide
• CAS: 1369534-86-0
• 化学式: C₂₁H₁₅F₃N₂O
• 分子量: 368.358
• InChiKey: AHCKRCSYRQEYFJ-BQJQTIKASA-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：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(4-trifluoromethylphenyl)-2-propen-1-ol 在 manganese(IV) oxide 、 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 38.0h， 生成 (2E,4E)-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

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.