2-[8-Fluoro-2-(2-formyl-3-{5-[5-(2-hydroxy-1,1-dimethyl-ethoxy)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-2-methyl-propionitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-[8-Fluoro-2-(2-formyl-3-{5-[5-(2-hydroxy-1,1-dimethyl-ethoxy)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-2-methyl-propionitrile
• 英文别名: 2-[8-fluoro-2-[2-formyl-3-[5-[[5-(1-hydroxy-2-methylpropan-2-yl)oxypyridin-2-yl]amino]-1-methyl-6-oxopyridazin-3-yl]phenyl]-1-oxoisoquinolin-6-yl]-2-methylpropanenitrile
• 化学式: C₃₄H₃₁FN₆O₅
• 分子量: 622.6
• InChiKey: RGYYAGYYYIAQOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  6-chloro-4-(5-(1-hydroxy-2-methylpropan-2-yloxy)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one 、 联硼酸频那醇酯 、 potassium acetate 、 2-二环己基磷-2,4,6-三异丙基联苯 、 2-[2-(3-bromo-2-formylphenyl)-8-fluoro-1-oxo-1,2-dihydroisoquinolin-6-yl]-2-methylpropionitrile 、 potassium carbonate 在 醋酸钯 、 Pd(dibenzylideneacetone)₂ 氩 、 乙酸乙酯 、 silica 、 silica gel 、 甲醇 、 二氯甲烷 作用下， 以 1,4-二氧六环 、 正丁醇 、 水 为溶剂， 反应 1.25h， 以to get 2-[8-fluoro-2-(2-formyl-3-{5-[5-(2-hydroxy-1,1-dimethyl-ethoxy)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-2-methyl-propionitrile (1.1 g, 57.38%, 400 mg mixture) as brown sticky solid的产率得到2-[8-Fluoro-2-(2-formyl-3-{5-[5-(2-hydroxy-1,1-dimethyl-ethoxy)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-2-methyl-propionitrile
  参考文献：
  名称：

  INHIBITORS OF BRUTON'S TYROSINE KINASE

  摘要：

  本申请公开了按通用式(I)定义的化合物，其中所有变量如本文所述，可抑制BTK。本文所披露的化合物有助于调节BTK的活性，治疗与过度BTK活性有关的疾病。这些化合物还有助于治疗与异常B细胞增殖有关的炎症和自身免疫性疾病，如类风湿性关节炎。还披露了含有通式I的化合物和至少一种载体、稀释剂或赋形剂的组合物。

  公开号：

  US20150376166A1

文献信息

• US9663494B2
  申请人：——

  公开号：US9663494B2

  公开（公告）日：2017-05-30
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014135474A1

  公开（公告）日：2014-09-12

  This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit BTK. The compounds disclosed herein are useful to modulate the activity of BTK and treat diseases associated with excessive BTK activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formula I and at least one carrier, diluent or excipient.
• INHIBITORS OF BRUTON'S TYROSINE KINASE
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20150376166A1

  公开（公告）日：2015-12-31

  This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit BTK. The compounds disclosed herein are useful to modulate the activity of BTK and treat diseases associated with excessive BTK activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formula I and at least one carrier, diluent or excipient.

  本申请公开了按通用式(I)定义的化合物，其中所有变量如本文所述，可抑制BTK。本文所披露的化合物有助于调节BTK的活性，治疗与过度BTK活性有关的疾病。这些化合物还有助于治疗与异常B细胞增殖有关的炎症和自身免疫性疾病，如类风湿性关节炎。还披露了含有通式I的化合物和至少一种载体、稀释剂或赋形剂的组合物。