(R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl-ammonium trifluoroacetate | 1415969-24-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl-ammonium trifluoroacetate
• 英文别名: 1-((R)-2-amino-3,3-dimethyl-butyryl)-azetidine-3-carbonitrile trifluoroacetate；1-[(2R)-2-amino-3,3-dimethylbutanoyl]azetidine-3-carbonitrile;2,2,2-trifluoroacetic acid
• CAS: 1415969-24-2
• 化学式: C₂HF₃O₂*C₁₀H₁₇N₃O
• 分子量: 309.288
• InChiKey: WMEIHTCCCQNXJB-QRPNPIFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.98
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-cyclopropyl-5-((2-trimethylsilanyl)ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-carboxylic acid 、 (R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl-ammonium trifluoroacetate 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以85%的产率得到2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylicacid [(R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl]-amide
  参考文献：
  名称：

  3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models

  摘要：

  The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.

  DOI：

  10.1021/jm301646k
• 作为产物：
  描述：

  叔丁氧羰基-D-叔亮氨酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 (R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl-ammonium trifluoroacetate
  参考文献：
  名称：

  [EN] PYRROLOPYRAZINE KINASE INHIBITORS
  [FR] INHIBITEURS DE PYRROLOPYRAZINE KINASE

  摘要：

  本发明涉及式I的新型吡咯并吡嗪衍生物的使用，其中变量如本文所述定义，其抑制JAK和SYK，并可用于治疗自身免疫和炎症性疾病。

  公开号：

  WO2013030138A1

文献信息

• Pyrrolopyrazine kinase inhibitors
  申请人：Chen Shaoqing

  公开号：US08658646B2

  公开（公告）日：2014-02-25

  The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用式I中新型吡咯吡嗪衍生物，其中变量如本文所述，其抑制JAK和SYK并且用于治疗自身免疫和炎症性疾病。
• PYRROLOPYRAZINE KINASE INHIBITORS
  申请人：Chen Shaoqing

  公开号：US20130059834A1

  公开（公告）日：2013-03-07

  The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用新型吡咯吡嗪衍生物（式I）的使用，其中变量如此处所述，其抑制JAK和SYK并且适用于治疗自身免疫和炎症性疾病。
• US8658646B2
  申请人：——

  公开号：US8658646B2

  公开（公告）日：2014-02-25
• [EN] PYRROLOPYRAZINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PYRROLOPYRAZINE KINASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013030138A1

  公开（公告）日：2013-03-07

  The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及式I的新型吡咯并吡嗪衍生物的使用，其中变量如本文所述定义，其抑制JAK和SYK，并可用于治疗自身免疫和炎症性疾病。
• 3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models
  作者：Michael Soth、Johannes C. Hermann、Calvin Yee、Muzaffar Alam、Jim W. Barnett、Pamela Berry、Michelle F. Browner、Karl Frank、Sandra Frauchiger、Seth Harris、Yang He、Mohammad Hekmat-Nejad、Than Hendricks、Robert Henningsen、Ramona Hilgenkamp、Hoangdung Ho、Ann Hoffman、Pei-Yuan Hsu、Dong-Qing Hu、Andrea Itano、Saul Jaime-Figueroa、Alam Jahangir、Sue Jin、Andreas Kuglstatter、Alan K. Kutach、Cheng Liao、Stephen Lynch、John Menke、Linghao Niu、Vaishali Patel、Aruna Railkar、Douglas Roy、Ada Shao、David Shaw、Sandra Steiner、Yongliang Sun、Seng-Lai Tan、Sandra Wang、Minh Diem Vu

  DOI：10.1021/jm301646k

  日期：2013.1.10

  The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.