5-amino-1-(2,6-difluorophenyl)-1H-pyrazole-4-carbaldehyde | 1080562-66-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-1-(2,6-difluorophenyl)-1H-pyrazole-4-carbaldehyde
• 英文别名: 5-amino-1-(2,6-difluorophenyl)pyrazole-4-carbaldehyde
• CAS: 1080562-66-8
• 化学式: C₁₀H₇F₂N₃O
• 分子量: 223.182
• InChiKey: SXNRMINIGWRQAJ-UHFFFAOYSA-N

物化性质

• 熔点：
  169.7-170.5 °C
• 沸点：
  378.7±42.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-amino-1-(2,6-difluorophenyl)-1H-pyrazole-4-carbaldehyde 在 哌啶 、 N-溴代丁二酰亚胺(NBS) 、 lithium acetate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 13.0h， 生成 5-bromo-1-(2,6-difluorophenyl)-1H-pyrazolo[3,4-b]pyridin-6(7H)-one
  参考文献：
  名称：

  Development of a Practical Synthesis of a Pyrazolopyridinone-Based p38 MAP Kinase Inhibitor

  摘要：

  A practical synthesis of the pyrazolopyridinone-based p38 MAP kinase inhibitor (4) was required for an ongoing program. The synthesis of a key pyrazolopyridinone building block was refined and optimized to provide kilogram quantities of 10 without chromatography or extractive workups. An efficient building-block strategy was employed to give optimal control of the key quality attributes, and in situ Raman spectroscopy was used to monitor and understand the complex solid-state properties of 4.

  DOI：

  10.1021/op100205s
• 作为产物：
  描述：

  4-hydroxy-2-oxotetrahydrofuran-3-yl 2-(2-(2,6-difluorophenyl)hydrazineyl)-2-oxoacetate 在 甲烷磺酸 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 溶剂黄146 、 乙腈 为溶剂， 20.0~80.0 ℃ 、204.76 kPa 条件下， 反应 6.83h， 生成 5-amino-1-(2,6-difluorophenyl)-1H-pyrazole-4-carbaldehyde
  参考文献：
  名称：

  Development of a Practical Synthesis of a Pyrazolopyridinone-Based p38 MAP Kinase Inhibitor

  摘要：

  A practical synthesis of the pyrazolopyridinone-based p38 MAP kinase inhibitor (4) was required for an ongoing program. The synthesis of a key pyrazolopyridinone building block was refined and optimized to provide kilogram quantities of 10 without chromatography or extractive workups. An efficient building-block strategy was employed to give optimal control of the key quality attributes, and in situ Raman spectroscopy was used to monitor and understand the complex solid-state properties of 4.

  DOI：

  10.1021/op100205s

文献信息

• Pyrazolo-pyridinone compounds and methods of use thereof
  申请人：Pettus Liping

  公开号：US20090012299A1

  公开（公告）日：2009-01-08

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , B, R 1 , R 2 , R 3 , R 4 and R 5 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of P38 map kinase mediated diseases including rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disease, pain and other inflammatory disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一类新化合物，可用于预防和治疗蛋白激酶介导的疾病，包括炎症和相关病症。该化合物具有通用的I式，其中A1、A2、A3、A4、B、R1、R2、R3、R4和R5的定义如下。本发明还包括制备I式化合物的中间体和方法，以及包括一种或多种I式化合物的药物组合物，用于治疗P38地图激酶介导的疾病，包括类风湿性关节炎、银屑病、慢性阻塞性肺疾病、疼痛和其他炎症性疾病。
• PYRAZOLO-PYRIDINONE AND PYRAZOLO-PYRAZINONE COMPOUNDS AS P38 MODULATORS AND METHODS OF USE THEREOF
  申请人：PETTUS Liping H.

  公开号：US20110294805A1

  公开（公告）日：2011-12-01

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , B, R 1 , R 2 , R 4 , R 5 , R 6 and Z are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of P38 map kinase mediated diseases including rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disease, pain and other inflammatory disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症和相关疾病。该化合物具有一般的化学式 I，其中 A1、A2、B、R1、R2、R4、R5、R6 和 Z 在本文中有定义。本发明还包括含有一种或多种化合物的制药组合物，以及用于治疗 P38 地图激酶介导的疾病，包括类风湿性关节炎、牛皮癣、慢性阻塞性肺疾病、疼痛和其他炎症性疾病的化合物和组合物的用途，以及用于制备化合物的中间体和过程。
• Pyrazolo-pyridinone and pyrazolo-pyrazinone compounds as P38 modulators and methods of use thereof
  申请人：Pettus Liping H.

  公开号：US20110105498A1

  公开（公告）日：2011-05-05

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , B, R 1 , R 2 , R 4 , R 5 , R 6 and Z are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of P38 map kinase mediated diseases including rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disease, pain and other inflammatory disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一类新化合物，可用于预防和治疗蛋白激酶介导的疾病，包括炎症和相关疾病。该化合物具有一般式I，其中A1、A2、B、R1、R2、R4、R5、R6和Z在本文中有定义。本发明还包括包括一种或多种I式化合物的制药组合物，以及用于治疗P38地图激酶介导的疾病，包括类风湿性关节炎、银屑病、慢性阻塞性肺疾病、疼痛和其他炎症性疾病的用途，以及用于制备I式化合物的中间体和过程。
• Discovery and Evaluation of 7-Alkyl-1,5-bis-aryl-pyrazolopyridinones as Highly Potent, Selective, and Orally Efficacious Inhibitors of p38α Mitogen-Activated Protein Kinase^⊥⊥ Atomic coordinates and structure factors for crystal structure of compound<b>3d</b>with p38α can be accessed using PDB code 3LHJ.
  作者：Liping H. Pettus、Ryan P. Wurz、Shimin Xu、Brad Herberich、Bradley Henkle、Qiurong Liu、Helen J. McBride、Sharon Mu、Matthew H. Plant、Christiaan J. M. Saris、Lisa Sherman、Lu Min Wong、Samer Chmait、Matthew R. Lee、Christopher Mohr、Faye Hsieh、Andrew S. Tasker

  DOI：10.1021/jm100095x

  日期：2010.4.8

  The p38 alpha mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1 beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38 alpha inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED50 <= 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.
• WO2008/136948
  申请人：——

  公开号：——

  公开（公告）日：——