3-氨基-N-甲氧基-4-甲基苯甲酰胺 | 427878-12-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氨基-N-甲氧基-4-甲基苯甲酰胺
• 英文名称: 3-amino-N-methoxy-4-methylbenzamide
• 英文别名: 3-amino-N-methoxy-4-methyl-benzamide；N-methoxy-3-amino-4-methylbenzamide
• CAS: 427878-12-4
• 化学式: C₉H₁₂N₂O₂
• 分子量: 180.206
• InChiKey: SQIYHQDCDNQPPX-UHFFFAOYSA-N

物化性质

• 密度：
  1.164±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-氨基-N-甲氧基-4-甲基苯甲酰胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 N-ethyl 4-((5-(methoxycarbamoyl)-2-methylphenyl)-amino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide
  参考文献：
  名称：

  Development of a Practical Synthesis of a p38 Kinase Inhibitor via a Safe and Robust Amination

  摘要：

  The development of a practical synthesis for a p38 kinase inhibitor is described. The key advances include an improved route to the key intermediate, a substituted pyrrole, and a subsequent animation utilizing O-(4-nitrobenzoyl)-hydroxylamine, which provides a safe, scalable, and robust amination method. The new protocol was successfully demonstrated to generate 1.6 kg of API in seven steps and 26% overall yield.

  DOI：

  10.1021/op300181r

文献信息

• [EN] 5-MEMBERED HETEROCYCLE-BASED P38 KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA KINASE P38 A BASE D'HETEROCYCLES A 5 CHAINONS
  申请人：TRIAD THERAPEUCTICS INC

  公开号：WO2005009973A1

  公开（公告）日：2005-02-03

  Provided are 5-membered heterocycle-based p38 kinase inhibitors. Further provided are pyrazole and imidazole-based p38 kinase, including p38α and p38β kinase, inhibitors. Pharmaceutical compositions containing the compounds are also provided. Methods of use of the compounds and compositions are also provided, including method of treatment, prevention, or amelioration of one or more symptoms of p38 kinase mediated diseases and disorders, including, but not limited to, inflammatory diseases and disorders.

  提供了基于5-成员杂环的p38激酶抑制剂。进一步提供了基于吡唑和咪唑的p38激酶抑制剂，包括p38α和p38β激酶。还提供了含有这些化合物的药物组合物。还提供了这些化合物和组合物的使用方法，包括治疗、预防或改善p38激酶介导的疾病和疾病的一个或多个症状的方法，包括但不限于炎症性疾病和疾病。
• The Discovery of Orally Active Triaminotriazine Aniline Amides as Inhibitors of p38 MAP Kinase
  作者：Katerina Leftheris、Gulzar Ahmed、Ran Chan、Alaric J. Dyckman、Zahid Hussain、Kan Ho、John Hynes,、Jeffrey Letourneau、Wei Li、Shuqun Lin、Axel Metzger、Kevin J. Moriarty、Chris Riviello、Yvonne Shimshock、James Wen、John Wityak、Stephen T. Wrobleski、Hong Wu、Junjun Wu、Madhuri Desai、Kathleen M. Gillooly、Tsung H. Lin、Derek Loo、Kim W. McIntyre、Sidney Pitt、Ding Ren Shen、David J. Shuster、Rosemary Zhang、David Diller、Arthur Doweyko、John Sack、Jack Baldwin、Joel Barrish、John Dodd、Ian Henderson、Steve Kanner、Gary L. Schieven、Maria Webb

  DOI：10.1021/jm049521d

  日期：2004.12.1

  A new structural class of triaminotriazine aniline amides possessing potent p38 enzyme activity has been discovered. The initial hit (compound 1a) was identified through screening the Pharmacopeia ECLiPS compound collection. SAR modification led to the identification of a short acting triaminotriazine aniline methoxyamide (compound 1m) possessing in vitro and in vivo oral activity in animal models

  已发现具有有效的p38酶活性的三氨基三嗪苯胺酰胺的新结构类别。通过筛选药典ECLiPS化合物集合来鉴定最初的化合物（化合物1a）。SAR修饰导致鉴定出在急性和慢性炎症性疾病动物模型中具有体外和体内口服活性的短效三氨基三嗪苯胺甲氧基酰胺（化合物1m）。与未激活的p38α蛋白共结晶的此类化合物1m的X射线晶体结构表明，这些化合物与ATP结合袋结合并在更深的裂隙中具有关键的H键相互作用。三嗪氮之一与Met109残基的主链NH之间的氢键通过水分子发生。
• ERK INHIBITORS AND USES THEREOF
  申请人：Celgene Avilomics Research, Inc.

  公开号：US20140228322A1

  公开（公告）日：2014-08-14

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用它们的方法。
• N-heterocyclic inhibitors of TNF-alpha expression
  申请人：——

  公开号：US20030139435A1

  公开（公告）日：2003-07-24

  N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula (I): 1 Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-&agr; expression utilizing compounds of the present invention are also disclosed.

  本发明揭示了通过抑制p38激酶来阻断细胞因子产生的N-杂环化合物。在一种实施方式中，本发明的化合物由式(I)表示。还公开了利用本发明的化合物生产方法、制药组合物以及治疗与不当p38激酶活性或TNF-α表达相关的疾病的方法。
• P-38 inhibitors
  申请人：——

  公开号：US20040254236A1

  公开（公告）日：2004-12-16

  Provided are 5-membered heterocycle-based p38 kinase, including p38&agr; and p38&bgr; kinase, inhibitors. Pharmaceutical compositions containing the compounds are also provided. Methods of use of the compounds and compositions are also provided, including methods of treatment, prevention, or amelioration of one or more symptoms of p38 kinase mediated diseases and disorders, including, but not limited to, inflammatory diseases and disorders.

  提供了基于5-成员杂环的p38激酶抑制剂，包括p38&agr;和p38&bgr;激酶。还提供了含有这些化合物的药物组合物。还提供了这些化合物和组合物的使用方法，包括治疗、预防或改善p38激酶介导的疾病和障碍的一个或多个症状的方法，包括但不限于炎症性疾病和障碍。