3-甲氧基-n-甲基-4-硝基苯甲酰胺 | 878160-13-5

• 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-甲氧基-n-甲基-4-硝基苯甲酰胺
• 英文名称: 3-methoxy-N-methyl-4-nitrobenzamide
• CAS: 878160-13-5
• 化学式: C₉H₁₀N₂O₄
• 分子量: 210.189
• InChiKey: AOQDJNLPLPYKIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 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：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-甲氧基-n-甲基-4-硝基苯甲酰胺 在 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 23.0h， 生成 2-methoxy-4-(4-methyl-4H-1,2,4-triazol-3-yl)aniline
  参考文献：
  名称：

  Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4-d]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N²-(2-Ethoxy-4-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-methyl-N⁸-neopentylpyrido[3,4-d]pyrimidine-2,8-diamine (BOS172722)

  摘要：

  Monopolar spindle 1 (MPS1) occupies a central role in mitosis and is one of the main components of the spindle assembly checkpoint. The MPS1 kinase is an attractive cancer target, and herein, we report the discovery of the clinical candidate BOS172722. The starting point for our work was a series of pyrido[3,4-d]pyrimidine inhibitors that demonstrated excellent potency and kinase selectivity but suffered from rapid turnover in human liver microsomes (HLM). Optimizing HLM stability proved challenging since it was not possible to identify a consistent site of metabolism and lowering lipophilicity proved unsuccessful. Key to overcoming this problem was the finding that introduction of a methyl group at the 6-position of the pyrido[3,4-d]pyrimidine core significantly improved HLM stability. Met ID studies suggested that the methyl group suppressed metabolism at the distant aniline portion of the molecule, likely by blocking the preferred pharmacophore through which P450 recognized the compound. This work ultimately led to the discovery of BOS172722 as a Phase 1 clinical candidate.

  DOI：

  10.1021/acs.jmedchem.8b00690
• 作为产物：
  描述：

  3-氟-4-硝基苯甲酸 在 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.17h， 生成 3-甲氧基-n-甲基-4-硝基苯甲酰胺
  参考文献：
  名称：

  WO2006/136402

  摘要：

  公开号：

文献信息

• [EN] INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS
  申请人：CANCER REC TECH LTD

  公开号：WO2014037750A1

  公开（公告）日：2014-03-13

  The present invention relates to compounds of formula (I), wherein R, R, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 – also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式(I)的化合物，其中R、R、Ar、W、X和Z均如本文所定义。本发明的化合物已知可以通过直接或间接地与Mps1激酶本身相互作用来抑制单丝粒体1（Mps1，也称为TTK）激酶的纺锤体检查点功能。具体而言，本发明涉及将这些化合物用作治疗和/或预防增殖性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的方法，以及包含它们的药物组合物。
• [EN] NOVEL PYRROLO[3,2-c]PYRIDINE-6-AMINO DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE PYRROLO[3,2-C]PYRIDINE-6-AMINO
  申请人：CANCER RES TECH LTD

  公开号：WO2017109476A1

  公开（公告）日：2017-06-29

  The present invention relates to novel pyrrolo[3,2-c]pyridine-6-amino derivatives that inhibit the spindle checkpoint function of Monospindle 1 (Mps1 – also known as TTK) kinases. In particular, the present invention relates to isopropyl 6-(2-methoxy-4-(1-5 methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2- c]pyridine-1-carboxylate and isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5- yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate and their use as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the 10 preparation of these compounds and to pharmaceutical compositions comprising them.

  本发明涉及一种新的吡咯并[3,2-c]吡啶-6-氨基衍生物，其抑制单丝粒体1（Mps1 - 也称为TTK）激酶的纺锤体检查点功能。具体而言，本发明涉及异丙基6-(2-甲氧基-4-(1-5 甲基-1H-1,2,3-三唑-5-基)苯胺基)-2-(1-甲基-1H-吡唑-4-基)-1H-吡咯并[3,2-c]吡啶-1-羧酸异丙酯和异丙基6-(2-甲氧基-4-(1-甲基-1H-四唑-5- 基)苯胺基)-2-(1-甲基-1H-吡唑-4-基)-1H-吡咯并[3,2-c]吡啶-1-羧酸异丙酯及其作为治疗和/或预防增殖性疾病（如癌症）的治疗剂的用途。本发明还涉及制备这些化合物的方法以及包含它们的药物组合物。
• THIENOPYRIMIDINES FOR PHARMACEUTICAL COMPOSITIONS
  申请人：Taylor Steven

  公开号：US20100143341A1

  公开（公告）日：2010-06-10

  The present invention relates to novel pharmaceutical compositions of general formula (I) comprising thienopyrimidine compounds. Moreover, the present invention relates to the use of the thienopyrimidine compounds of the invention for the production of pharmaceutical compositions for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.

  本发明涉及通式（I）的新型药物组合物，其包括噻唑嘧啶化合物。此外，本发明涉及使用本发明的噻唑嘧啶化合物生产药物组合物，用于预防和/或治疗可以通过抑制Mnk1和/或Mnk2（Mnk2a或Mnk2b）及/或其变体的激酶活性而受到影响的疾病。
• Peg-based adhesive phenylic derivatives and methods of synthesis and use
  申请人：MURPHY John L.

  公开号：US20160032047A1

  公开（公告）日：2016-02-04

  The invention provides compositions that use phenylic derivatives to provide adhesive properties. Selection of phenylic derivatives with linkers or linking groups, and the linkages between the linkers or linking groups with polyalkylene oxides, provided herein may be configured to control curing time, biodegradation and/or swelling.

  本发明提供了使用苯基衍生物作为黏合剂的组合物。本发明提供了苯基衍生物与连接剂或连接基团的选择，以及连接剂或连接基团与聚烷氧化物之间的连接，可以配置以控制固化时间、生物降解和/或肿胀。
• INHIBITOR COMPOUNDS
  申请人：CANCER RESEARCH TECHNOLOGY

  公开号：US20150239884A1

  公开（公告）日：2015-08-27

  The present invention relates to compounds of formula I wherein R 1 , R 4 , Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式I的化合物，其中R1、R4、Ar、W、X和Z均如本文所定义。本发明的化合物已知能够直接或间接地通过与Mps1激酶本身的相互作用来抑制单纺锤体1（Mps1，也称为TTK）激酶的纺锤体检查点功能。特别地，本发明涉及使用这些化合物作为治疗和/或预防增生性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的过程，以及包含它们的药物组合物。