(1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-(4-(methylthio)phenyl)propan-2-amine | 1028527-85-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-(4-(methylthio)phenyl)propan-2-amine
• 英文别名: (1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine；(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-methylsulfanylphenyl)propan-2-amine
• CAS: 1028527-85-6
• 化学式: C₂₃H₂₂FN₃OS
• 分子量: 407.512
• InChiKey: MZPGOAFFXBWDPN-WNSKOXEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 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：
  78.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-(4-(methylthio)phenyl)propan-2-amine 、 乙酰氧基乙酰氯 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以0.7 g的产率得到2-(((1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-(4-(methylthio)phenyl)propan-2-yl)amino)-2-oxoethyl acetate
  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
• 作为产物：
  描述：

  2-氟-5-碘苯甲醛 在 copper(l) iodide 、 caesium carbonate 作用下， 反应 22.0h， 生成 (1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-(4-(methylthio)phenyl)propan-2-amine
  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
  申请人：Berger Markus

  公开号：US20080207721A1

  公开（公告）日：2008-08-28

  Compounds of formula (I): or a pharmaceutically acceptable salt thereof, compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating the glucocorticoid receptor in a warm blooded animal).

  化学式为（I）的化合物或其药学上可接受的盐、包含它们的组合物、制备它们的过程以及它们在医疗治疗中的应用（例如在温血动物中调节糖皮质激素受体）。
• 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。
• CHEMICAL COMPOUNDS
  申请人：Berger Markus

  公开号：US20120065173A1

  公开（公告）日：2012-03-15

  Compounds of formula (I): or a pharmaceutically acceptable salt thereof; compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating the glucocorticoid receptor in a warm blooded animal).

  式(I)的化合物或其药学上可接受的盐；包含它们的组合物；制备它们的过程以及它们在医疗治疗中的应用（例如调节温血动物的糖皮质激素受体）。
• Indazolyl sulphonamide derivatives useful as glucocorticoid modulators
  申请人：AstraZeneca AB

  公开号：US08030340B2

  公开（公告）日：2011-10-04

  Compounds of formula (I): or a pharmaceutically acceptable salt thereof, compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating the glucocorticoid receptor in a warm blooded animal).

  化学式为(I)的化合物或其药学上可接受的盐，包括它们的组合物，制备它们的过程以及它们在医学治疗中的应用（例如在温血动物中调节糖皮质激素受体）。