2-(3,5-dichlorophenylamino)-4-trifluoromethylpyrimidine-5-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(3,5-dichlorophenylamino)-4-trifluoromethylpyrimidine-5-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amide
• 英文别名: 2-(3,5-dichlorophenylamino)-4-trifluoromethylpyrimidine-5-carboxylic acid (tetrahydropyran-4-ylmethyl)-amide；2-(3,5-dichlorophenylamino)-4-trifluoromethylpyrimidine-5-carboxylic acid (tetrahydropyran-4-ylmethyl)amide；2-(3,5-dichlorophenylamino)-4-trifluoromethylpyrimidine-5-carboxylic acid N-(tetrahydropyran-4-ylmethyl)amide；2-(3,5-dichloroanilino)-N-(oxan-4-ylmethyl)-4-(trifluoromethyl)pyrimidine-5-carboxamide
• 化学式: C₁₈H₁₇Cl₂F₃N₄O₂
• 分子量: 449.26
• InChiKey: APBBPNOWHFPBMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  76.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氨甲基四氢吡喃 、 2-(3,5-dichlorophenylamino)-4-trifluoromethyl-pyrimidine-5-carboxylic acid 在 N-乙基吗啉 、 1-羟基苯并三唑一水物 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以68 mg的产率得到2-(3,5-dichlorophenylamino)-4-trifluoromethylpyrimidine-5-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amide
  参考文献：
  名称：

  Discovery of 2-[(2,4-Dichlorophenyl)amino]-N-[(tetrahydro- 2H-pyran-4-yl)methyl]-4-(trifluoromethyl)- 5-pyrimidinecarboxamide, a Selective CB2 Receptor Agonist for the Treatment of Inflammatory Pain

  摘要：

  Selective CB2 receptor agonists are promising potential therapeutic agents for the treatment of inflammatory and neuropathic pain. A focused screen identified a pyrimidine ester as a partial agonist at the CB2 receptor with micromolar potency. Subsequent lead optimization identified 35, GW842166X, as the optimal compound in the series. 35 has an oral ED50 of 0.1 mg/kg in the rat FCA model of inflammatory pain and was selected as a clinical candidate for this indication.

  DOI：

  10.1021/jm061195+

文献信息

• Pyrimidine Derivatives And Their Use As CB2 Modulators
  申请人：Eatherton Andrew John

  公开号：US20100041654A1

  公开（公告）日：2010-02-18

  This relates to novel pyrimidine derivatives, pharmaceutical compositions containing these compounds and their use in the treatment of diseases, particularly pain, which diseases are caused directly or indirectly by an increase or decrease in activity of the cannabinoid receptor.

  本发明涉及新的嘧啶衍生物、含有这些化合物的药物组合物以及它们在治疗疾病中的应用，特别是治疗由于大麻素受体活性增加或减少而直接或间接引起的疼痛等疾病。
• US7635701B2
  申请人：——

  公开号：US7635701B2

  公开（公告）日：2009-12-22
• Discovery of 2-[(2,4-Dichlorophenyl)amino]-<i>N</i>-[(tetrahydro- 2<i>H</i>-pyran-4-yl)methyl]-4-(trifluoromethyl)- 5-pyrimidinecarboxamide, a Selective CB2 Receptor Agonist for the Treatment of Inflammatory Pain
  作者：Gerard M. P. Giblin、Celestine T. O'Shaughnessy、Alan Naylor、William L. Mitchell、Andrew J. Eatherton、Brian P. Slingsby、D. Anthony Rawlings、Paul Goldsmith、Andrew J. Brown、Carl P. Haslam、Nick M. Clayton、Alex W. Wilson、Iain P. Chessell、Andrew R. Wittington、Richard Green

  DOI：10.1021/jm061195+

  日期：2007.5.1

  Selective CB2 receptor agonists are promising potential therapeutic agents for the treatment of inflammatory and neuropathic pain. A focused screen identified a pyrimidine ester as a partial agonist at the CB2 receptor with micromolar potency. Subsequent lead optimization identified 35, GW842166X, as the optimal compound in the series. 35 has an oral ED50 of 0.1 mg/kg in the rat FCA model of inflammatory pain and was selected as a clinical candidate for this indication.