2-[[4-chloro-3-(trifluoromethyl)phenyl]methylene]hydrazinecarboximidamide hydrochloride | 849335-07-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[[4-chloro-3-(trifluoromethyl)phenyl]methylene]hydrazinecarboximidamide hydrochloride
• 英文别名: CFMHC；AC-3099；2-(4-chloro-3-(trifluoromethyl)benzylidene)hydrazinecarboximidamide hydrochloride；1-[4-Chloro-3-(trifluoromethyl)benzylideneamino]guanidine Hydrochloride；2-[[4-chloro-3-(trifluoromethyl)phenyl]methylideneamino]guanidine;hydrochloride
• CAS: 849335-07-5
• 化学式: C₉H₈ClF₃N₄*ClH
• 分子量: 301.098
• InChiKey: OMYOUCJVJYJITH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.39
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  76.8
• 氢给体数：
  3
• 氢受体数：
  5

制备方法与用途

AC-099盐酸盐（化合物3）是一种选择性NPFF2R全激动剂（EC50＝1189 nM），同时也是NPFF1R的部分激动剂（EC250＝2370 nM）。研究显示，AC-099盐酸盐能够减轻大鼠脊髓神经结扎引起的超敏反应。

反应信息

• 作为产物：
  描述：

  3-三氟甲基-4-溴苯甲醛 、 肼甲酰亚胺酰胺一氯化氢 以 乙醇 为溶剂， 反应 18.0h， 以87%的产率得到2-[[4-chloro-3-(trifluoromethyl)phenyl]methylene]hydrazinecarboximidamide hydrochloride
  参考文献：
  名称：

  Discovery of Selective Nonpeptidergic Neuropeptide FF2 Receptor Agonists

  摘要：

  We report the discovery and initial characterization of a novel class of selective NPFF2 agonists. HTS screening using R-SAT, a whole cell based functional assay, identified a class of aryliminoguanidines as NPFF1 and NPFF2 ligands. Subsequent optimization led to molecules exhibiting selective NPFF2 agonistic activity. Systemic administration showed that selective NPFF2 agonists (1 and 3)are active in various pain models in vivo, whereas administration of it nonselective NPFF1 and NPFF2 agonist (9) increases sensitivity to noxious and non-noxious stimuli.

  DOI：

  10.1021/jm9011998

文献信息

• Aminoguanidine Hydrazone Derivatives as Nonpeptide NPFF1 Receptor Antagonists Reverse Opioid Induced Hyperalgesia
  作者：Hassan Hammoud、Khadija Elhabazi、Raphäelle Quillet、Isabelle Bertin、Valérie Utard、Emilie Laboureyras、Jean-Jacques Bourguignon、Frédéric Bihel、Guy Simonnet、Frédéric Simonin、Martine Schmitt

  DOI：10.1021/acschemneuro.8b00099

  日期：2018.11.21

  this work, we sought to identify novel NPFF receptors ligands by focusing our interest in a series of heterocycles as rigidified nonpeptide NPFF receptor ligands, starting from already described aminoguanidine hydrazones (AGHs). Binding experiments and functional assays highlighted AGH 1n and its rigidified analogue 2-amino-dihydropyrimidine 22e for in vivo experiments. As shown earlier with the prototypical

  先前已显示神经肽FF受体（NPFF1R和NPFF2R）及其内源性配体神经肽FF具有抗阿片类药物的特性，并且在鸦片类药物长期服用相关的不良反应中起关键作用，包括阿片类药物引起的痛觉过敏和镇痛耐受性的发展。在这项工作中，我们试图通过将我们的注意力集中在一系列杂环上来鉴定新的NPFF受体配体，这些杂环作为刚性化的非肽NPFF受体配体，从已经描述的氨基胍（AGH）开始。结合实验和功能测定突出了用于体内实验的AGH 1n及其刚性化类似物2-氨基-二氢嘧啶22e。如先前使用原型二肽拮抗剂RF9所示，1n和22e均显着降低了芬太尼诱导的鼠持久性痛觉过敏。总而言之，这些数据表明，AGH硬化对两种NPFF受体均保持纳摩尔亲和力，同时改善了对NPFF1R的拮抗特性。
• Treating neuropathic pain with neuropeptide FF receptor 2 agonists
  申请人：Scully L. Audra

  公开号：US20050136444A1

  公开（公告）日：2005-06-23

  The invention described below relates to the discovery of the neuropeptide FF receptor subtype that mediates acute nociception and chronic neuropathic pain, compounds that selectively interact with this receptor subtype and methods for treating acute pain and chronic neuropathic pain.

  以下所描述的发明涉及到发现了介导急性痛觉和慢性神经病理性疼痛的神经肽FF受体亚型、与该受体亚型有选择性相互作用的化合物以及治疗急性疼痛和慢性神经病理性疼痛的方法。
• Discovery of Selective Nonpeptidergic Neuropeptide FF2 Receptor Agonists
  作者：Gilles Gaubert、Fabio Bertozzi、Nicholas M. Kelly、Jan Pawlas、Audra L. Scully、Norman R. Nash、Luis R. Gardell、Jelveh Lameh、Roger Olsson

  DOI：10.1021/jm9011998

  日期：2009.11.12

  We report the discovery and initial characterization of a novel class of selective NPFF2 agonists. HTS screening using R-SAT, a whole cell based functional assay, identified a class of aryliminoguanidines as NPFF1 and NPFF2 ligands. Subsequent optimization led to molecules exhibiting selective NPFF2 agonistic activity. Systemic administration showed that selective NPFF2 agonists (1 and 3)are active in various pain models in vivo, whereas administration of it nonselective NPFF1 and NPFF2 agonist (9) increases sensitivity to noxious and non-noxious stimuli.