tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

• 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: tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate
• 英文别名: tert-butyl N-[(1S,2R)-2-[[6-carbamoyl-5-[(5-fluoro-6-methylpyridin-2-yl)amino]pyridazin-3-yl]amino]cyclohexyl]carbamate
• 化学式: C₂₂H₃₀FN₇O₃
• 分子量: 459.524
• InChiKey: ADIJHJYJJYXAGZ-CABCVRRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate 在 三氟乙酸 作用下， 以 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 为溶剂， 反应 3.0h， 以32%的产率得到6-((1R,2S)-2-aminocyclohexylamino)-4-(5-fluoro-6-methylpyridin-2-ylamino)pyridazine-3-carboxamide
  参考文献：
  名称：

  Using Ovality to Predict Nonmutagenic, Orally Efficacious Pyridazine Amides as Cell Specific Spleen Tyrosine Kinase Inhibitors

  摘要：

  Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of cancers and autoimmune diseases such as asthma, rheumatoid arthritis, and systemic lupus erythematous. We report the structure-guided optimization of pyridazine amide spleen tyrosine kinase inhibitors. Early representatives of this scaffold were highly potent and selective but mutagenic in an Ames assay. An approach that led to the successful identification of nonmutagenic examples, as well as further optimization to compounds with reduced cardiovascular liabilities is described. Select pharmacokinetic and in vivo efficacy data are presented.

  DOI：

  10.1021/jm401982j
• 作为产物：
  描述：

  2-氨基-5-氟-6-甲基吡啶 在 4-二甲氨基吡啶 、 氨 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙腈 为溶剂， 反应 114.0h， 生成 tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate
  参考文献：
  名称：

  PYRIDAZINE AMIDE COMPOUNDS

  摘要：

  本发明涉及使用式I的新型三唑吡啶衍生物，其中所有变量取代基如本文所述，这些化合物是SYK抑制剂，可用于治疗自身免疫和炎症性疾病。

  公开号：

  US20130178478A1

文献信息

• Pyridazine amide compounds useful as SYK inhibitors
  申请人：Hoffmann-La Roche Inc.

  公开号：US08901124B2

  公开（公告）日：2014-12-02

  The present invention relates to the use of novel triazolopyridine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用以下式I的新型三唑并[3,4-b]吡啶衍生物，其中所有变量取代基的定义如本文所述，这些衍生物为SYK抑制剂，可用于治疗自身免疫和炎症性疾病。
• PYRIDAZINE AMIDE COMPOUNDS AND THEIR USE AS SYK INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2802567B1

  公开（公告）日：2017-03-01
• US8901124B2
  申请人：——

  公开号：US8901124B2

  公开（公告）日：2014-12-02
• [EN] PYRIDAZINE AMIDE COMPOUNDS AND THEIR USE AS SYK INHIBITORS<br/>[FR] COMPOSÉS DE PYRIDAZINAMIDE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE SYK
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013104573A1

  公开（公告）日：2013-07-18

  The present invention relates to the use of novel triazolopyridine derivatives of formula (I): wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.
• Using Ovality to Predict Nonmutagenic, Orally Efficacious Pyridazine Amides as Cell Specific Spleen Tyrosine Kinase Inhibitors
  作者：Matthew C. Lucas、Niala Bhagirath、Eric Chiao、David M. Goldstein、Johannes C. Hermann、Pei-Yuan Hsu、Stephan Kirchner、Joshua J. Kennedy-Smith、Andreas Kuglstatter、Christine Lukacs、John Menke、Linghao Niu、Fernando Padilla、Ying Peng、Liudmila Polonchuk、Aruna Railkar、Michelle Slade、Michael Soth、Daigen Xu、Preeti Yadava、Calvin Yee、Mingyan Zhou、Cheng Liao

  DOI：10.1021/jm401982j

  日期：2014.3.27

  Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of cancers and autoimmune diseases such as asthma, rheumatoid arthritis, and systemic lupus erythematous. We report the structure-guided optimization of pyridazine amide spleen tyrosine kinase inhibitors. Early representatives of this scaffold were highly potent and selective but mutagenic in an Ames assay. An approach that led to the successful identification of nonmutagenic examples, as well as further optimization to compounds with reduced cardiovascular liabilities is described. Select pharmacokinetic and in vivo efficacy data are presented.