(1R,2S)-2-amino-1-(6-methoxypyridin-3-yl)propan-1-ol | 1196452-56-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1R,2S)-2-amino-1-(6-methoxypyridin-3-yl)propan-1-ol
• 英文别名: (1R,2S)-2-Amino-1-[6-methoxypyridin-3-yl]propan-1-ol
• CAS: 1196452-56-8
• 化学式: C₉H₁₄N₂O₂
• 分子量: 182.222
• InChiKey: XNFRRHNIDGUZSA-RCOVLWMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  68.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2S)-2-amino-1-(6-methoxypyridin-3-yl)propan-1-ol 在 copper(l) iodide 、 trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II) 、 N,N-二甲基甘氨酸 、 tri tert-butylphosphoniumtetrafluoroborate caesium carbonate 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 丁腈 为溶剂， 反应 93.17h， 生成 3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(6-methoxypyridin-3-yl)propyl]oxy}-1H-indazol-1-yl)-N-(pyridin-3-ylmethyl)benzamide
  参考文献：
  名称：

  [EN] PHENYL OR PYRIDINYL SUBSTITUTED INDAZOLES DERIVATIVES
  [FR] DÉRIVÉS INDAZOLES À SUBSTITUTION PHÉNYL OU PYRIDINYLE

  摘要：

  一种化合物的化学式Ia：公式（Ia）。本发明涉及新型吲唑基衍生物，包括这种衍生物的药物组合物，制备这种新型衍生物的方法以及将这种衍生物用作药物的用途。

  公开号：

  WO2009142569A1
• 作为产物：
  描述：

  5-溴-2-甲氧基吡啶 在 盐酸 、 异丙基氯化镁 、 aluminum isopropoxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 异丙醇 为溶剂， 反应 20.5h， 生成 (1R,2S)-2-amino-1-(6-methoxypyridin-3-yl)propan-1-ol
  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：US20120252770A1

  公开（公告）日：2012-10-04

  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

  化学式(I)的化合物：本发明涉及新型的吲哚基酯或酰胺衍生物，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，以及这些衍生物作为药物的用途。
• Phenyl or Pyridinyl Substituted Indazoles Derivatives
  申请人：Berger Markus

  公开号：US20100080786A1

  公开（公告）日：2010-04-01

  A compound of formula Ia: The present invention relates to novel indazolyl derivatives, to pharmaceutical compositions comprising such derivatives, to processes for preparing such novel derivatives and to the use of such derivatives as medicaments

  一种化学式Ia的化合物：本发明涉及新颖的吲哚啉衍生物，包括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。
• Discovery of a Novel Oral Glucocorticoid Receptor Modulator (AZD9567) with Improved Side Effect Profile
  作者：Lena Ripa、Karl Edman、Matthew Dearman、Goran Edenro、Ramon Hendrickx、Victoria Ullah、Hui-Fang Chang、Matti Lepistö、Dave Chapman、Stefan Geschwindner、Lisa Wissler、Petter Svanberg、Karolina Lawitz、Jesper Malmberg、Antonios Nikitidis、Roine I. Olsson、James Bird、Antoni Llinas、Tove Hegelund-Myrbäck、Markus Berger、Philip Thorne、Richard Harrison、Christian Köhler、Tomas Drmota

  DOI：10.1021/acs.jmedchem.7b01690

  日期：2018.3.8

  Synthetic glucocorticoids (GC) are essential for the treatment of a broad range of inflammatory diseases. However, their use is limited by target related adverse effects on, e.g., glucose homeostasis and bone metabolism. Starting from a nonsteroidal GR ligand (4) that is a full agonist in reporter gene assays, we exploited key functional triggers within the receptor, generating a range of structurally diverse partial agonists. Of these, only a narrow subset exhibited full anti-inflammatory efficacy and a significantly reduced impact on adverse effect markers in human cell assays compared to prednisolone. This led to the discovery of AZD9567 (15) with excellent in vivo efficacy when dosed orally in a rat model of joint inflammation. Compound 15 is currently being evaluated in clinical trials comparing the efficacy and side effect markers with those of prednisolone.
• Discovery of indazole ethers as novel, potent, non-steroidal glucocorticoid receptor modulators
  作者：Martin Hemmerling、Karl Edman、Matti Lepistö、Anders Eriksson、Svetlana Ivanova、Jan Dahmén、Hartmut Rehwinkel、Markus Berger、Ramon Hendrickx、Matthew Dearman、Tina Jellesmark Jensen、Lisa Wissler、Thomas Hansson

  DOI：10.1016/j.bmcl.2016.10.052

  日期：2016.12

  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.
• [EN] PHENYL OR PYRIDINYL SUBSTITUTED INDAZOLES DERIVATIVES<br/>[FR] DÉRIVÉS INDAZOLES À SUBSTITUTION PHÉNYL OU PYRIDINYLE
  申请人：ASTRAZENECA AB

  公开号：WO2009142569A1

  公开（公告）日：2009-11-26

  A compound of formula Ia: Formula (la) The present invention relates to novel indazolyl derivatives, to pharmaceutical compositions comprising such derivatives, to processes for preparing such novel derivatives and to the use of such derivatives as medicaments.

  一种化合物的化学式Ia：公式（Ia）。本发明涉及新型吲唑基衍生物，包括这种衍生物的药物组合物，制备这种新型衍生物的方法以及将这种衍生物用作药物的用途。