2,2,2-trifluoro-N-((1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-phenylpropan-2-yl)acetamide | 1034148-00-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2,2,2-trifluoro-N-((1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-phenylpropan-2-yl)acetamide
• 英文别名: 2,2,2-trifluoro-N-((1S,2R)-2-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-methyl-2-phenylethyl)acetamide；2,2,2-Trifluoro-N-[(1r,2s)-1-{[1-(4-Fluorophenyl)-1h-Indazol-5-Yl]oxy}-1-Phenylpropan-2-Yl]acetamide；2,2,2-trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-phenylpropan-2-yl]acetamide
• CAS: 1034148-00-9
• 化学式: C₂₄H₁₉F₄N₃O₂
• 分子量: 457.427
• InChiKey: UITKQZZSZUEHEA-NYHFZMIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氟-5-碘苯甲醛 在 copper(l) iodide 、 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 19.5h， 生成 2,2,2-trifluoro-N-((1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-phenylpropan-2-yl)acetamide
  参考文献：
  名称：

  Discovery of indazole ethers as novel, potent, non-steroidal glucocorticoid receptor modulators

  摘要：

  A structure-based design approach led to the identification of a novel class of indazole ether based, nonsteroidal glucocorticoid receptor (GR) modulators. Several examples were identified that displayed cell potency in the picomolar range, inhibiting LPS-induced TNF-alpha release by primary peripheral blood mononuclear cells (PBMCs). Additionally, an improved steroid hormone receptor binding selectivity profile, compared to classical steroidal GR agonists, was demonstrated. The indazole ether core tolerated a broad range of substituents allowing for modulation of the physiochemical parameters. A small subset of indazole ethers, with pharmacokinetic properties suitable for oral administration, was investigated in a rat antigen-induced joint inflammation model and demonstrated excellent anti-inflammatory efficacy. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.052

文献信息

• Chemical compounds 572
  申请人：Berger Markus

  公开号：US20080214641A1

  公开（公告）日：2008-09-04

  Compounds of formula (I): The present invention relates to novel indazolyl ester or amide derivatives, to pharmaceutical compositions comprising such derivatives, to processes for preparing such novel derivatives and to the use of such derivatives as medicaments

  化合物公式（I）：本发明涉及新型吲唑酯或酰胺衍生物，涉及包含这些衍生物的制药组合物，涉及制备这些新型衍生物的过程，以及将这些衍生物用作药物的用途。
• Chemical Compounds 572
  申请人：Berger Markus

  公开号：US20100197644A1

  公开（公告）日：2010-08-05

  Compounds of formula (I): The present invention relates to novel indazolyl ester or amide derivatives, to pharmaceutical compositions comprising such derivatives, to processes for preparing such novel derivatives and to the use of such derivatives as medicaments

  式(I)的化合物：本发明涉及新型吲哚酰基或酰胺衍生物，以及包含这些衍生物的制药组合物，制备这些新型衍生物的方法以及将这些衍生物用作药物的用途。
• INDAZOLYL ESTER AND AMIDE DERIVATIVES FOR THE TREATMENT OF GLUCOCORTICOID RECEPTOR MEDIATED DISORDERS
  申请人：AstraZeneca AB

  公开号：EP2102169A1

  公开（公告）日：2009-09-23
• INDAZOLYL AMIDE DERIVATIVES FOR THE TREATMENT OF GLUCOCORTICOID RECEPTOR MEDIATED DISORDERS
  申请人：AstraZeneca AB

  公开号：EP2102169B1

  公开（公告）日：2012-06-20
• US7728030B2
  申请人：——

  公开号：US7728030B2

  公开（公告）日：2010-06-01