N-(1-phenylpyrazol-3-yl)-N-(1-phenethyl-4-piperidyl)amine | 425644-16-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(1-phenylpyrazol-3-yl)-N-(1-phenethyl-4-piperidyl)amine
• 英文别名: 1-phenethyl-N-(1-phenyl-1H-pyrazol-3-yl)piperidin-4-amine；Fbj3QU2fyb；1-(2-phenylethyl)-N-(1-phenylpyrazol-3-yl)piperidin-4-amine
• CAS: 425644-16-2
• 化学式: C₂₂H₂₆N₄
• 分子量: 346.475
• InChiKey: NQBQHIOBBPNVSM-UHFFFAOYSA-N

物化性质

• 沸点：
  515.4±45.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  丙酸酐 、 N-(1-phenylpyrazol-3-yl)-N-(1-phenethyl-4-piperidyl)amine 反应 4.0h， 以55%的产率得到N-[1-(2-phenylethyl)-4-piperidyl]-N-(1-phenyl-4-pyrazolyl)propanamide
  参考文献：
  名称：

  长效芬太尼类似物：N-（1-苯基吡唑基）-N-（1-苯基烷基-4-哌啶基）丙酰胺的合成和药理作用。

  摘要：

  描述了新的芬太尼类似物的合成，其中丙腈基的苯环已被苯基吡唑代替。使用扭体试验和热板试验在小鼠中评估抗伤害感受活性。两种化合物显示出令人感兴趣的镇痛特性，比吗啡强，比芬太尼强，但作用时间更长。这些化合物抑制了豚鼠回肠和小鼠输精管的电诱发的肌肉收缩，但没有抑制兔输精管的电诱发的肌肉收缩，并且可以被拮抗剂（纳洛酮和/或CTOP）逆转，因此表明这些化合物起到了mu激动剂的作用。最后，结合数据证实了该化合物对mu受体具有高亲和力和选择性。

  DOI：

  10.1016/s0968-0896(01)00345-5
• 作为产物：
  描述：

  3-氨基-4,5-二氢-1-苯基吡唑 在 对甲苯磺酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 21.5h， 生成 N-(1-phenylpyrazol-3-yl)-N-(1-phenethyl-4-piperidyl)amine
  参考文献：
  名称：

  长效芬太尼类似物：N-（1-苯基吡唑基）-N-（1-苯基烷基-4-哌啶基）丙酰胺的合成和药理作用。

  摘要：

  描述了新的芬太尼类似物的合成，其中丙腈基的苯环已被苯基吡唑代替。使用扭体试验和热板试验在小鼠中评估抗伤害感受活性。两种化合物显示出令人感兴趣的镇痛特性，比吗啡强，比芬太尼强，但作用时间更长。这些化合物抑制了豚鼠回肠和小鼠输精管的电诱发的肌肉收缩，但没有抑制兔输精管的电诱发的肌肉收缩，并且可以被拮抗剂（纳洛酮和/或CTOP）逆转，因此表明这些化合物起到了mu激动剂的作用。最后，结合数据证实了该化合物对mu受体具有高亲和力和选择性。

  DOI：

  10.1016/s0968-0896(01)00345-5

文献信息

• Arylamide derivatives having multimodal activity against pain
  申请人：ESTEVE PHARMACEUTICALS, S.A.

  公开号：US10577360B2

  公开（公告）日：2020-03-03

  The present invention relates to arylamide derivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

  本发明涉及对电压门控钙通道的α2δ亚基（尤其是α2δ-1亚基）和μ-阿片受体具有双重药理活性的芳酰胺衍生物，涉及此类化合物的制备工艺，涉及含有此类化合物的药物组合物，还涉及此类化合物在治疗中的用途，尤其是用于治疗疼痛。
• Synthesis and opioid activity of new fentanyl analogs
  作者：Rocı́o Girón、Raquel Abalo、Carlos Goicoechea、Ma Isabel Martı́n、Luis F Callado、Carolina Cano、Pilar Goya、Nadine Jagerovic

  DOI：10.1016/s0024-3205(02)01798-8

  日期：2002.7

  Three new fentanyl analogs (compounds 3-4-5) have been synthesized and evaluated for antinociceptive properties using the writhing test. The analgesic property of the active compound, N-[1-phenylpyrazol-3-yl]-N-[1-(2-phenethyl)-4-piperidyl)] propenamide (compound 4), was tested using the hot plate test in mice. Its opioid agonistic activity was characterized using three isolated tissues: guinea pig ileum, mouse vas deferens, and rabbit vas deferens. Compound 4 was as effective as fentanyl or morphine and it showed less antinociceptive potency than fentanyl but it was more potent than morphine. The duration of the antinociception was similar to that of fentanyl. This compound inhibited the electrically evoked contractions of myenteric plexus-longitudinal muscle strips of guinea pig ileum and of mouse vas deferens but not those of rabbit vas deferens. These effects could be reversed by mu selective antagonists (naloxone and/or CTOP) but not by the delta selective antagonist naltrindole, thus indicating that the compound acted as a mu opioid agonist. Finally, the binding data confirmed that compound 4 had high affinity and selectivity for the mu-receptor. (C) 2002 Published by Elsevier Science Inc.
• ARYLAMIDE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN
  申请人：ESTEVE PHARMACEUTICALS , S.A.

  公开号：US20190127357A1

  公开（公告）日：2019-05-02

  The present invention relates to arylamide derivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.