N-cyclopropyl-4-methyl-3-(7-methyl-6-oxo-1-o-tolyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide | 1080572-12-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-cyclopropyl-4-methyl-3-(7-methyl-6-oxo-1-o-tolyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide
• 英文别名: N-cyclopropyl-4-methyl-3-[7-methyl-1-(2-methylphenyl)-6-oxopyrazolo[3,4-b]pyridin-5-yl]benzamide
• CAS: 1080572-12-8
• 化学式: C₂₅H₂₄N₄O₂
• 分子量: 412.491
• InChiKey: GPNGBBAQRLTFSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)benzamide 、 5-bromo-7-methyl-1-o-tolyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.5h， 生成 N-cyclopropyl-4-methyl-3-(7-methyl-6-oxo-1-o-tolyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide
  参考文献：
  名称：

  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 compound3dwith p38α can be accessed using PDB code 3LHJ.

  摘要：

  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.

  DOI：

  10.1021/jm100095x

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 COMPOUNDS, PROCESS FOR THEIR PREPARATION, AND THEIR PHARMACEUTICAL USE
  申请人：Amgen, Inc

  公开号：EP2152704A1

  公开（公告）日：2010-02-17
• US7846944B2
  申请人：——

  公开号：US7846944B2

  公开（公告）日：2010-12-07
• [EN] PYRAZOLO-PYRIDINONE COMPOUNDS, PROCESS FOR THEIR PREPARATION, AND THEIR PHARMACEUTICAL USE<br/>[FR] COMPOSÉS PYRAZOLO-PYRIDINONE, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR PROCÉDÉ D'UTILISATION PHARMACEUTIQUE
  申请人：AMGEN INC

  公开号：WO2008137176A1

  公开（公告）日：2008-11-13

  [EN] 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, A², A³, A⁴, B, R¹, R², R³, R⁴ and R⁵ 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.
  [FR] L'invention concerne une nouvelle classe de composés servant à la prophylaxie et au traitement de maladies médiées par des protéines kinases, notamment une inflammation et des troubles associés. Les composés de l'invention sont représentés par la formule (I). Dans cette formule, A¹, A², A³, A⁴, B, R¹, R², R³, R⁴ et R⁵ sont définis dans la description. L'invention concerne également des compositions pharmaceutiques comprenant au moins un composé de formule (I), des procédés d'utilisation de tels composés et des compositions pour traiter des maladies médiées par des P38 map-kinases comme l'arthrite rhumatoïde, le psoriasis, les maladies pulmonaires obstructives chroniques, la douleur et d'autres troubles inflammatoires. L'invention concerne également des intermédiaires et des procédés servant à préparer des composés de formule (I).
• 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.