5-amino-1-(2,6-difluorophenyl)-1H-pyrazole-4-carbonitrile | 1188285-05-3

• 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-carbonitrile
• 英文别名: 5-amino-1-(2,6-difluorophenyl)pyrazole-4-carbonitrile
• CAS: 1188285-05-3
• 化学式: C₁₀H₆F₂N₄
• 分子量: 220.181
• InChiKey: XBBQLCCTQJHMIC-UHFFFAOYSA-N

物化性质

• 熔点：
  130-131 °C
• 沸点：
  395.1±42.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.6
• 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-carbonitrile 在 ice 、 乙酸乙酯 、 Brine 作用下， 以 盐酸 为溶剂， 反应 10.0h， 以to afford 1-(2,6-difluorophenyl)-1H-pyrazol-5-amine as a brown amorphous solid的产率得到1-(2,6-difluorophenyl)-1H-pyrazol-5-amine
  参考文献：
  名称：

  Pyrazolo-Pyrazinone Compounds and Methods of Use Thereof

  摘要：

  本发明涉及一类新的化合物，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。该化合物具有一般的化学式I，其中A1、B、R1、R2、R3、R4、R5和n在此定义。本发明还包括含有一种或多种化合物I的药物组合物，以及用于治疗p38 MAP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化合物和组合物的用途，以及用于制备化合物I的中间体和工艺。

  公开号：

  US20110105499A1
• 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 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 0.33h， 生成 5-amino-1-(2,6-difluorophenyl)-1H-pyrazole-4-carbonitrile
  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

• [EN] GLUCOSE TRANSPORT INHIBITORS<br/>[FR] INHIBITEURS DE TRANSPORT DU GLUCOSE
  申请人：BAYER PHARMA AG

  公开号：WO2013182612A1

  公开（公告）日：2013-12-12

  The present invention relates to chemical compounds of general formula (I): in which RA, RB, RC, RD, m, and n are as given in the description and in the claims, and which effectively and selectively inhibit glucose transporter 1 (GLUT1), to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

  本发明涉及通式(I)的化合物：其中RA、RB、RC、RD、m和n如描述和权利要求中所述，并且有效地且选择性地抑制葡萄糖转运蛋白1（GLUT1），以及制备该化合物的方法，包括含有该化合物的药物组合物和药物组合物，以及利用该化合物制造用于治疗或预防疾病的药物组合物的用途，以及在制备该化合物中有用的中间体化合物。
• [EN] PYRAZOLO-PYRAZINONE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS DE PYRAZOLO-PYRAZINONES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2009117156A1

  公开（公告）日：2009-09-24

  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 A1, B, R1, R2, R3, R4, R5 and n 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，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。这些化合物具有一般的化学式（I），其中A1、B、R1、R2、R3、R4、R5和n在此处定义。该发明还涉及包括一种或多种化合物的药物组合物，以及用于治疗p38 MAP激酶介导的疾病，包括类风湿关节炎、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工艺。
• Pyrazolo[3.4-B]pyrazine compounds as p38 modulators and methods of use as anti-inflamatory agents
  申请人：Tasker Andrew

  公开号：US08367671B2

  公开（公告）日：2013-02-05

  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 A1, B, R1, R2, R3, R4, R5 and n 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.

  本发明涉及一类新型化合物，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。该化合物具有通用的I式，其中A1、B、R1、R2、R3、R4、R5和n在此定义。本发明还包括包括一个或多个I式化合物的制药组合物，以及用于治疗p38 map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.
• US8367671B2
  申请人：——

  公开号：US8367671B2

  公开（公告）日：2013-02-05