methyl 5-trichloromethyl-3-methyl-1H-pyrazole-1-carboxylate | 1105612-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 5-trichloromethyl-3-methyl-1H-pyrazole-1-carboxylate
• 英文别名: methyl 3-methyl-5-(trichloromethyl)-1H-pyrazole-1-carboxylate；MPClE
• CAS: 1105612-57-4
• 化学式: C₇H₇Cl₃N₂O₂
• 分子量: 257.504
• InChiKey: UWEHKOZAHNWCKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.63
• 重原子数：
  14.0
• 可旋转键数：
  0.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.12
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  肼基甲酸甲酯 、 1,1,1-trichloro-4-methoxy-3-penten-2-one 生成 methyl 5-trichloromethyl-3-methyl-1H-pyrazole-1-carboxylate
  参考文献：
  名称：

  A novel, potent, oral active and safe antinociceptive pyrazole targeting kappa opioid receptors

  摘要：

  Pyrazole compounds are an intriguing class of compounds with potential analgesic activity; however, their mechanism of action remains unknown. Thus, the goal of this study was to explore the antinociceptive potential, safety and mechanism of action of novel 1-pyrazole methyl ester derivatives, which were designed by molecular simplification, using in vivo and in vitro methods in mice. First, tree 1-pyrazole methyl ester derivatives (DMPE, MPFE, and MPCIE) were tested in the capsaicin test and all presented antinociceptive effect; however the MPCIE (methyl 5-trichloromethyl-3-methyl-1H-pyrazolel-carboxylate) was the most effective. Thus, we selected this compound to assess the effects and mechanisms in subsequent pain models. MPCIE produced antinociception when administered by oral, intraperitoneal, intrathecal and intraplantar routes and was effective in the capsaicin and the acetic acid-induced nociception tests. Moreover, this compound reduced the hyperalgesia in diverse clinically-relevant pain models, including postoperative, inflammatory, and neuropathic nociception in mice. The antinociception produced by orally administered MPCIE was mediated by kappa-opioid receptors, since these effects were prevented by systemically pre-treatment with naloxone and the kappa-opioid receptor antagonist nor-binaltorphimine. Moreover, MPCIE prevented binding of the kappa-opioid ligand [H-3]-CI-977 in vitro (IC50 of 0.68 (032-1.4) mu M), but not the TRPV1 ([H-3]-resiniferatoxin) or the alpha(2)-adrenoreceptor ([H-3]-idazoxan) binding. Regarding the drug-induced side effects, oral administration of MPCIE did not produce sedation, constipation or motor impairment at its active dose. In addition, MPCIE was readily absorbed after oral administration. Taken together, these results demonstrate that MPCIE is a novel, potent, orally active and safe analgesic drug that targets kappa-opioid receptors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.neuropharm.2013.06.011