methyl 5-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 5-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carboxylate
• 英文别名: methyl 5-tosylpyrrolo[2,3-b]pyrazine-2-carboxylate；methyl 5-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyrazine-2-carboxylate
• 化学式: C₁₅H₁₃N₃O₄S
• 分子量: 331.352
• InChiKey: HOXIJDBMDNNOQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  99.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 5-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carboxylate 在 劳森试剂 、 盐酸 、 dipotassium hydrogenphosphate 、 叠氮磷酸二苯酯 、 10 wt% Pd(OH)2 on carbon 、 水 、 氢气 、 sodium hydride 、 三乙胺 、 三氟乙酸 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 乌帕替尼
  参考文献：
  名称：

  Upadacitinib tartrate. Tyrosine-protein kinase JAK1 inhibitor, Treatment of autoimmune inflammatory diseases, Treatment of rheumatoid arthritis

  摘要：

  Upadacitinib tartrate (ABT-494) is a potent and selective tyrosine-protein kinase JAK1 inhibitor being developed for the treatment of systemic autoimmune inflammatory diseases, including rheumatoid arthritis (RA), Crohn's disease, ulcerative colitis and psoriatic arthritis. In vitro, upadacitinib demonstrated higher selectivity for inhibiting JAK1 over JAK2 and JAK3, suggesting a potentially improved therapeutic profile in treating patients with inflammatory diseases compared to nonselective JAK inhibitors. Upadacitinib has demonstrated safety and efficacy in phase II trials in patients with RA and inflammatory bowel disease, and is currently in phase III development for these indications.

  DOI：

  10.1358/dof.2018.043.10.2849626
• 作为产物：
  描述：

  5-溴-4,7-二氮杂吲哚 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 5-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carboxylate
  参考文献：
  名称：

  Upadacitinib tartrate. Tyrosine-protein kinase JAK1 inhibitor, Treatment of autoimmune inflammatory diseases, Treatment of rheumatoid arthritis

  摘要：

  Upadacitinib tartrate (ABT-494) is a potent and selective tyrosine-protein kinase JAK1 inhibitor being developed for the treatment of systemic autoimmune inflammatory diseases, including rheumatoid arthritis (RA), Crohn's disease, ulcerative colitis and psoriatic arthritis. In vitro, upadacitinib demonstrated higher selectivity for inhibiting JAK1 over JAK2 and JAK3, suggesting a potentially improved therapeutic profile in treating patients with inflammatory diseases compared to nonselective JAK inhibitors. Upadacitinib has demonstrated safety and efficacy in phase II trials in patients with RA and inflammatory bowel disease, and is currently in phase III development for these indications.

  DOI：

  10.1358/dof.2018.043.10.2849626

文献信息

• Novel Tricyclic Compounds
  申请人：Wishart Neil

  公开号：US20090312338A1

  公开（公告）日：2009-12-17

  The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

  这项发明提供了一个符合Formula (I)的化合物，其中包括药用盐、前药、生物活性代谢物、立体异构体和同分异构体，其中变量在此处定义。该发明的化合物对治疗免疫和肿瘤疾病有用。
• JAK1 SELECTIVE INHIBITOR AND USES THEREOF
  申请人：ABBVIE INC.

  公开号：US20150118229A1

  公开（公告）日：2015-04-30

  The invention relates to the use of a JAK1 kinase-selective inhibitor that has minimal inhibitory activity towards Jak2 kinase for treating a disease, such as an inflammatory disease (e.g., moderate to severe Rheumatoid Arthritis) and/or bone loss, either alone or in combination with a DMARD (disease modifying anti-rheumatic drug), such as methotrexate. The invention also provides pharmaceutical composition, dosage formulation, administration route, and dosage schedule thereof.

  该发明涉及使用一种对JAK1激酶具有选择性抑制作用且对Jak2激酶的抑制活性最小的抑制剂来治疗疾病，例如炎症性疾病（例如中重度类风湿关节炎）和/或骨质流失，可以单独使用或与DMARD（疾病修饰性抗风湿药物）如甲氨蝶呤联合使用。该发明还提供了药物组合、剂量配方、给药途径和剂量方案。
• [EN] NOVEL TRICYCLIC COMPOUNDS<br/>[FR] COMPOSÉS TRICYCLIQUES INNOVANTS
  申请人：ABBOTT LAB

  公开号：WO2011068881A1

  公开（公告）日：2011-06-09

  The invention provides compounds of Formula (I) and Formula (II), pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

  该发明提供了Formula (I)和Formula (II)的化合物，以及在此定义的变量的药用可接受盐、前药、生物活性代谢物、立体异构体和同分异构体。该发明的化合物对于治疗免疫和肿瘤疾病是有用的。
• [EN] JAK1 SELECTIVE INHIBITOR AND USES THEREOF<br/>[FR] INHIBITEUR SÉLECTIF DE JAK1 ET SES UTILISATIONS
  申请人：ABBVIE INC

  公开号：WO2015061665A1

  公开（公告）日：2015-04-30

  The invention relates to the use of a JAKl kinase- selective inhibitor that has minimal inhibitory activity towards Jak2 kinase for treating a disease, such as an inflammatory disease (e.g., moderate to severe Rheumatoid Arthritis) and/or bone loss, either alone or in combination with a DMARD (disease modifying anti-rheumatic drug), such as methotrexate. The invention also provides pharmaceutical composition, dosage formulation, administration route, and dosage schedule thereof.

  本发明涉及使用一种对JAK1激酶选择性抑制剂，该抑制剂对JAK2激酶的抑制活性最小，用于治疗疾病，例如炎症性疾病（例如中度至重度类风湿性关节炎）和/或骨质流失，单独或与DMARD（疾病修饰抗风湿药物）如甲氨蝶呤联合使用。本发明还提供了药物组合物、剂量配方、给药途径和剂量方案。
• Tricyclic compounds
  申请人：Wishart Neil

  公开号：US08426411B2

  公开（公告）日：2013-04-23

  The invention provides compounds of Formula (I) and Formula (II) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

  本发明提供式(I)和式(II)的化合物，以及其药学上可接受的盐、前药、生物活性代谢物、立体异构体和同分异构体，其中变量在此定义。本发明的化合物可用于治疗免疫和肿瘤病症。