2,2-difluoro-N-[(1R,2S)-3-methyl-1-{[1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-indazol-5-yl]oxy}-1-phenylbutan-2-yl]propanamide | 1893415-00-3

• 物质功能分类: 医药中间体 - 杂环化合物
• 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: 2,2-difluoro-N-[(1R,2S)-3-methyl-1-{[1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-indazol-5-yl]oxy}-1-phenylbutan-2-yl]propanamide
• 英文别名: AZD9567；Azd9567；2,2-difluoro-N-[(1R,2S)-3-methyl-1-[1-(1-methyl-6-oxopyridin-3-yl)indazol-5-yl]oxy-1-phenylbutan-2-yl]propanamide
• CAS: 1893415-00-3
• 化学式: C₂₇H₂₈F₂N₄O₃
• 分子量: 494.541
• InChiKey: ZQFNDBISEYQVRR-LOSJGSFVSA-N

物化性质

• 沸点：
  629.3±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  76.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-碘-1H-吲唑 在 吡啶 、 盐酸 、 copper(l) iodide 、 N,N-二甲基甘氨酸 、 copper diacetate 、 potassium carbonate 、 caesium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 100.0h， 生成 2,2-difluoro-N-[(1R,2S)-3-methyl-1-{[1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-indazol-5-yl]oxy}-1-phenylbutan-2-yl]propanamide
  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

文献信息

• [EN] NEW PHYSICAL FORM<br/>[FR] NOUVELLE FORME PHYSIQUE
  申请人：ASTRAZENECA AB

  公开号：WO2017161518A1

  公开（公告）日：2017-09-28

  A crystalline form of 2, 2-difluoro-N- [ (1R, 2S) -3-methyl-1- [1- (1-methyl-6-oxo-1, 6-dihydropyridin-3-yl) -1H-indazol-5-yl] oxy} -1-phenylbutan-2-yl] propanamide (form C), pharmaceutical compositions containing it and its use in therapy.

  2,2-二氟-N-[(1R,2S)-3-甲基-1-[1-(1-甲基-6-氧代-1,6-二氢吡啶-3-基)-1H-吲哚-5-基]氧基}-1-苯基丁酰)-2-基]丙酰胺（C形式）的结晶形式，含有它的药物组合物以及其在治疗中的用途。
• [EN] PHYSICAL FORM OF A SGR MODULATOR<br/>[FR] FORME PHYSIQUE D'UN MODULATEUR SÉLECTIF DU RÉCEPTEUR DES GLUCOCORTICOÏDES
  申请人：ASTRAZENECA AB

  公开号：WO2017162747A1

  公开（公告）日：2017-09-28

  A crystalline form of 2,2-difluoro-N-[(1R,2S)-3-methyl-1-[1-(1-methyl-6-oxo-1,6- dihydropyridin-3-yl)-1H-indazol-5-yl]oxy}-1-phenylbutan-2-yl]propanamide (form C), pharmaceutical compositions containing it and its use in therapy.

  2,2-二氟-N-[(1R,2S)-3-甲基-1-[1-(1-甲基-6-氧代-1,6-二氢吡啶-3-基)-1H-吲唑-5-基]氧基}-1-苯基丁-2-基]丙酰胺（C型晶体形态），含有它的制药组合物以及它在治疗中的用途。
• 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。
• Physical form of a SGR modulator
  申请人：ASTRAZENECA AB

  公开号：US10407404B2

  公开（公告）日：2019-09-10

  A crystalline form of 2,2-difluoro-N-[(1R,2S)-3-methyl-1-[1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-indazol-5-yl]oxy}-1-phenylbutan-2-yl]propanamide (form C), pharmaceutical compositions containing it and its use in therapy.

  2,2-二氟-N-[(1R,2S)-3-甲基-1-[1-(1-甲基-6-氧代-1,6-二氢吡啶-3-基)-1H-吲唑-5-基]氧基}-1-苯基丁-2-基]丙酰胺（形式 C）的结晶形式、含有它的药物组合物及其在治疗中的应用。
• [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