5-iodo-1-(6-methoxypyridin-3-yl)-1H-indazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-iodo-1-(6-methoxypyridin-3-yl)-1H-indazole
• 英文别名: 5-Iodo-1-(6-methoxypyridin-3-yl)-1H-indazole；5-iodo-1-(6-methoxypyridin-3-yl)indazole
• 化学式: C₁₃H₁₀IN₃O
• 分子量: 351.146
• InChiKey: BKPANGHVSGGRAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-iodo-1-(6-methoxypyridin-3-yl)-1H-indazole 在 盐酸 、 copper(l) iodide 、 N,N-二甲基甘氨酸 、 potassium carbonate 、 caesium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 100.0h， 生成 5-(5-((1R,2S)-2-amino-3-methyl-1-phenylbutoxy)-1H-indazol-1-yl)-1-methylpyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of a Novel Oral Glucocorticoid Receptor Modulator (AZD9567) with Improved Side Effect Profile

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.7b01690
• 作为产物：
  描述：

  5-碘-1H-吲唑 、 2-甲氧基-5-吡啶硼酸 在 吡啶 、 copper diacetate 作用下， 以 二氯甲烷 为溶剂， 以86%的产率得到5-iodo-1-(6-methoxypyridin-3-yl)-1H-indazole
  参考文献：
  名称：

  [EN] 1-ALKYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL COMPOUNDS AND USE AS SGRM MODULATORS
  [FR] COMPOSÉS DE 1-ALKYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YLE ET LEUR UTILISATION COMME MODULATEURS SGRM

  摘要：

  公开号：

  WO2016046260A8

文献信息

• 1-alkyl-6-oxo-1,6-dihydropyridin-3-yl compounds and use as SGRM modulators
  申请人：AstraZeneca AB

  公开号：US10196374B2

  公开（公告）日：2019-02-05

  This specification generally relates to 1-alkyl-6-oxo-1,6-dihydropyridin-3-yl compounds (including salts thereof). This specification also relates to pharmaceutical compositions and kits comprising such a compound, uses of such a compound (including treatment methods and medicament preparations), and processes for making such a compound.

  本说明书一般涉及 1-烷基-6-氧代-1,6-二氢吡啶-3-基化合物（包括其盐）。本说明书还涉及包含此类化合物的药物组合物和试剂盒、此类化合物的用途（包括治疗方法和药物制剂）以及制造此类化合物的工艺。
• [EN] 1-ALKYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL COMPOUNDS AND USE AS SGRM MODULATORS<br/>[FR] COMPOSÉS DE 1-ALKYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YLE ET LEUR UTILISATION COMME MODULATEURS SGRM
  申请人：ASTRAZENECA AB

  公开号：WO2016046260A8

  公开（公告）日：2017-04-13
• 1-ALKYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL COMPOUNDS AND USE AS SGRM MODULATORS
  申请人：Astrazeneca

  公开号：EP3197878A1

  公开（公告）日：2017-08-02
• 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.