1,5-dimethyl-3-nitropyridin-2(1H)-one

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 1,5-dimethyl-3-nitropyridin-2(1H)-one
• 英文别名: 1,5-Dimethyl-3-nitro-pyridon-(2)；1,5-dimethyl-3-nitro-1H-pyridin-2-one；1,5-Dimethyl-3-nitropyridin-2-one
• 化学式: C₇H₈N₂O₃
• 分子量: 168.152
• InChiKey: WJSQXLBMGQUQPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,5-dimethyl-3-nitropyridin-2(1H)-one 在 palladium 10% on activated carbon 、 水 、 氢气 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.67h， 生成 4-((1,5-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)amino)-N,5-dimethylthieno[2,3-d]pyrimidine-6-carboxamide
  参考文献：
  名称：

  Discovery of 4-(dihydropyridinon-3-yl)amino-5-methylthieno[2,3-d]pyrimidine derivatives as potent Mnk inhibitors: synthesis, structure–activity relationship analysis and biological evaluation

  摘要：

  Phosphorylation of the eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) is essential for oncogenesis but unnecessary for normal development. Thus, pharmacological inhibition of Mnks may offer an effective and non-toxic anti-cancer therapeutic strategy. Herein, we report the discovery of 4-(dihydropyridinon-3-yl)amino-5-methylthieno[2,3-d]pyrimidine derivatives as potent Mnk inhibitors. Docking study of 7a in Mnk2 suggests that the compound is stabilised in the ATP binding site through multiple hydrogen bonds and hydrophobic interaction. Cellular mechanistic studies on MV-4-11 cells with leads 7a, 8e and 8f reveal that they are able to down-regulate the phosphorylated eIF4E, Mcl-1 and cyclin D1, and induce apoptosis. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.032
• 作为产物：
  描述：

  碘甲烷 、 2-羟基-5-甲基-3-硝基吡啶 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以95%的产率得到1,5-dimethyl-3-nitropyridin-2(1H)-one
  参考文献：
  名称：

  [EN] PYRROLIDIONE DERIVATIVES AS INHIBITORS OF NF KAPPA B INDUCING KINASE
  [FR] DÉRIVÉS DE PYRROLIDIONE UTILES COMME INHIBITEURS DE LA KINASE D'INDUCTION DE NF-KB

  摘要：

  本公开涉及抑制 NIK 的式 (I) 化合物和包含此类化合物的药物组合物以及使用方法。这些化合物和药物组合物可用于预防或治疗疾病，如但不限于炎症性疾病和自身免疫性疾病。

  公开号：

  WO2023217879A1

文献信息

• [EN] NEW 6-MEMBERED HETEROAROMATIC SUBSTITUTED CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE CYANOINDOLINE À SUBSTITUTION HÉTÉROAROMATIQUE À 6 CHAÎNONS UTILISÉS COMME INHIBITEURS DE NIK
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2017125534A1

  公开（公告）日：2017-07-27

  The present invention relates to pharmaceutical agents of formula (I), useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-KB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  本发明涉及公式（I）的药物制剂，用于治疗和/或预防哺乳动物，特别是用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病的NF-KB诱导激酶（NIK - 也称为MAP3K14）抑制剂。该发明还涉及包含这些化合物的药物组合物，以及利用这些化合物或药物组合物预防或治疗癌症、炎症性疾病、包括肥胖和糖尿病在内的代谢性疾病以及自身免疫性疾病的用途。
• Pyrazolopyrrolidine compounds
  申请人：Furet Pascal

  公开号：US08969341B2

  公开（公告）日：2015-03-03

  The invention relates to compounds of formula (I) as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of MDM2 and/or MDM4, and combinations comprising such compounds.

  本发明涉及式（I）所述的化合物，包括这种化合物的制药制剂，以及在治疗由MDM2和/或MDM4活性介导的疾病或疾患中使用这种化合物的用途和使用方法，以及包含这种化合物的组合物。
• Pyrazolopyrrolidine Compounds
  申请人：NOVARTIS AG

  公开号：US20140350010A1

  公开（公告）日：2014-11-27

  The invention relates to compounds of formula (I) as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of MDM2 and/or MDM4, and combinations comprising such compounds.

  本发明涉及公式（I）所描述的化合物，包括这些化合物的制药制剂，以及这些化合物在治疗由MDM2和/或MDM4活性介导的疾病或疾病中的使用和使用方法，以及包含这些化合物的组合物。
• 6-membered heteroaromatic substituted cyanoindoline derivatives as NIK inhibitors
  申请人：Janssen Pharmaceutica NV

  公开号：US11001569B2

  公开（公告）日：2021-05-11

  The present invention relates to pharmaceutical agents of formula (I), useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK—also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as a cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  本发明涉及式(I)的药物制剂，可用于哺乳动物的治疗和/或预防，尤其涉及NF-κB诱导激酶（NIK-又称MAP3K14）的抑制剂，可用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病等疾病。本发明还涉及包含此类化合物的药物组合物，以及使用此类化合物或药物组合物预防或治疗癌症、炎症性疾病、代谢紊乱（包括肥胖和糖尿病）和自身免疫性疾病等疾病。
• PYRAZOLOPYRROLIDINE COMPOUNDS
  申请人：Novartis AG

  公开号：EP2785717B1

  公开（公告）日：2016-01-13