6-tert-Butyl-8-fluoro-2-{3-[5-(1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-2H-phthalazin-1-one | 1360055-61-3

• 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: 6-tert-Butyl-8-fluoro-2-{3-[5-(1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-2H-phthalazin-1-one
• 英文别名: 6-tert-butyl-8-fluoro-2-{3-[5-(1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl]-2-(hydroxymethyl)phenyl}-2H-phthalazin-1-one；6-tert-butyl-8-fluoro-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(5-(piperidin-4-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)phthalazin-1(2H)-one；6-tert-butyl-8-fluoro-2-[2-(hydroxymethyl)-3-[1-methyl-6-oxo-5-[(5-piperidin-4-ylpyridin-2-yl)amino]pyridazin-3-yl]phenyl]phthalazin-1-one
• CAS: 1360055-61-3
• 化学式: C₃₄H₃₆FN₇O₃
• 分子量: 609.703
• InChiKey: LOFUVHPCQVWKPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  45
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,2,2-三氟乙基三氟甲烷磺酸酯 、 6-tert-Butyl-8-fluoro-2-{3-[5-(1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-2H-phthalazin-1-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以70%的产率得到6-tert-Butyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-6-oxo-5-[1'-(2,2,2-trifluoro-ethyl)-1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino]-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-one
  参考文献：
  名称：

  Inhibitors of Bruton's Tyrosine Kinase

  摘要：

  该应用程序根据通用公式I揭示了6-(2-羟甲基苯基)-2-甲基-2H-吡啶并-3-酮衍生物： 其中，变量X、R和Y4如本文所述定义，这些衍生物抑制Btk。本文披露的化合物可用于调节Btk的活性并治疗与过度Btk活性相关的疾病。这些化合物进一步可用于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，如类风湿性关节炎。还披露了含有公式I化合物和至少一种载体、稀释剂或赋形剂的组合物。

  公开号：

  US20120040949A1
• 作为产物：
  描述：

  tert-butyl 4-(6-(6-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate 在 trifluoro 、 乙酸乙酯 、 碳酸氢钠 、 Sodium sulfate-III 、 crude product 、 isopropylacetate hexanes 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以providing the desired product as a white solid (48 mg, 65.7%)的产率得到6-tert-Butyl-8-fluoro-2-{3-[5-(1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-2H-phthalazin-1-one
  参考文献：
  名称：

  Inhibitors of bruton's tyrosine kinase

  摘要：

  本申请披露了根据通用式I定义的6-(2-羟甲基苯基)-2-甲基-2H-吡啶并[3,4-d]嘧啶-3-酮衍生物，其中变量X，R和Y4如本文所述，可抑制Btk。本文披露的化合物可用于调节Btk的活性并治疗与过度Btk活性相关的疾病。这些化合物进一步可用于治疗与异常B细胞增殖相关的炎症和自身免疫性疾病，如类风湿性关节炎。本文还披露了含有通用式I化合物和至少一种载体、稀释剂或赋形剂的组合物。

  公开号：

  US08940741B2

文献信息

• INHIBITORS OF BRUTON'S TYROSINE KINASE
  申请人：Hoffmann-La Roche Inc.

  公开号：US20130178461A1

  公开（公告）日：2013-07-11

  This application discloses 6-(2-Hydroxymethyl-phenyl)-2-methyl-2H-pyridazin-3-one derivatives according to generic Formula I: wherein, variables X, R, and Y 4 , 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.

  本申请披露了根据通用式I定义的6-(2-羟甲基苯基)-2-甲基-2H-吡啶并[3,4-b][1,4]嗪衍生物，其中，变量X、R和Y4如本文所述，这些衍生物可抑制Btk。本申请所披露的化合物可用于调节Btk的活性并治疗与过度Btk活性相关的疾病。这些化合物还可用于治疗与异常B细胞增殖相关的炎症和自身免疫性疾病，例如类风湿性关节炎。本申请还披露了含有通用式I化合物和至少一种载体、稀释剂或赋形剂的组合物。
• US8481540B2
  申请人：——

  公开号：US8481540B2

  公开（公告）日：2013-07-09
• US8940741B2
  申请人：——

  公开号：US8940741B2

  公开（公告）日：2015-01-27
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012020008A1

  公开（公告）日：2012-02-16

  This application discloses 6-(2-Hydroxymethyl-phenyl)-2-methyl-2H-pyridazin-3-one derivatives according to generic Formula (I): wherein, variables X, R, and Y4, 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：Berthel Steven Joseph

  公开号：US20120040949A1

  公开（公告）日：2012-02-16

  This application discloses 6-(2-Hydroxymethyl-phenyl)-2-methyl-2H-pyridazin-3-one derivatives according to generic Formula I: wherein, variables X, R, and Y 4 , 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.

  该应用程序根据通用公式I揭示了6-(2-羟甲基苯基)-2-甲基-2H-吡啶并-3-酮衍生物： 其中，变量X、R和Y4如本文所述定义，这些衍生物抑制Btk。本文披露的化合物可用于调节Btk的活性并治疗与过度Btk活性相关的疾病。这些化合物进一步可用于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，如类风湿性关节炎。还披露了含有公式I化合物和至少一种载体、稀释剂或赋形剂的组合物。