4-Morpholino-6-oxo-1,6-dihydropyridin | 200064-43-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-Morpholino-6-oxo-1,6-dihydropyridin
• 英文别名: 4-morpholinopyridin-2(1H)-one；4-morpholin-4-yl-1H-pyridin-2-one
• CAS: 200064-43-3
• 化学式: C₉H₁₂N₂O₂
• 分子量: 180.206
• InChiKey: KZINEOWJVFJAIB-UHFFFAOYSA-N

物化性质

• 熔点：
  220-222 °C
• 沸点：
  378.0±42.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Morpholino-6-oxo-1,6-dihydropyridin 在 水 、 sodium hydride 、 lithium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 [4-(morpholin-4-yl)-2-oxo-2H-pyridin-1-yl]-acetic acid
  参考文献：
  名称：

  Development of peptidomimetic boronates as proteasome inhibitors

  摘要：

  Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (beta 5), trypsin-like (beta 2) and caspase-like (beta 1). Most important for the development of effective antitumor agents is the inhibition of the beta 5 subunits. In this context, the dipeptide boronate bortezomib (Velcade (R)) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide boronates (1-3) structurally related to bortezomib. The synthesized compounds showed a promising inhibitory profile by blocking primarily the chymotrypsin-like activity of the proteasome with K-i values in submicromolar/micromolar range. These compounds also resulted quite selective since no significant inhibition was recorded in the test against bovine pancreatic alpha-chymotrypsin. The obtained results were rationalized by means of docking experiments based on a model of the crystal structure of bortezomib bound to the yeast 20S proteasome providing essential insights for further optimization of this class of inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.032
• 作为产物：
  描述：

  2,4-二氯吡啶 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 potassium hydride 、 sodium t-butanolate 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， 反应 21.25h， 生成 4-Morpholino-6-oxo-1,6-dihydropyridin
  参考文献：
  名称：

  Development of peptidomimetic boronates as proteasome inhibitors

  摘要：

  Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (beta 5), trypsin-like (beta 2) and caspase-like (beta 1). Most important for the development of effective antitumor agents is the inhibition of the beta 5 subunits. In this context, the dipeptide boronate bortezomib (Velcade (R)) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide boronates (1-3) structurally related to bortezomib. The synthesized compounds showed a promising inhibitory profile by blocking primarily the chymotrypsin-like activity of the proteasome with K-i values in submicromolar/micromolar range. These compounds also resulted quite selective since no significant inhibition was recorded in the test against bovine pancreatic alpha-chymotrypsin. The obtained results were rationalized by means of docking experiments based on a model of the crystal structure of bortezomib bound to the yeast 20S proteasome providing essential insights for further optimization of this class of inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.032

文献信息

• 6-aryl-4-morpholin-1-ylpyridone compounds useful for the treatment of cancer and diabetes
  申请人：Sprint Bioscience AB

  公开号：US11077113B2

  公开（公告）日：2021-08-03

  The invention provides novel 6-aryl or 6-heteroaryl 4-morpholin-4-yl-pyhdine-2-one compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, diabetes, inflammatory diseases, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R1, R2, R3 and R4 are as defined in the specification.

  本发明提供了新颖的 6-芳基或 6-杂芳基 4-吗啉-4-基-吡啶-2-酮式（I）化合物、含有此类化合物的药物组合物以及使用此类化合物治疗包括癌症、糖尿病、炎症性疾病、神经退行性疾病、心血管疾病和病毒感染等疾病的方法；其中 R1、R2、R3 和 R4 如说明书中所定义。
• Vinter-Pasquier, Karine; Jamart-Gregoire, Brigitte; Caubere, Paul, Heterocycles, 1997, vol. 45, # 11, p. 2113 - 2129
  作者：Vinter-Pasquier, Karine、Jamart-Gregoire, Brigitte、Caubere, Paul

  DOI：——

  日期：——
• 6-ARYL-4-(MORPHOLIN-4-YL)-1H-PYRIDIN-2-ONE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER AND DIABETES
  申请人：Sprint Bioscience AB

  公开号：EP3416945B1

  公开（公告）日：2020-07-01
• 6-HETEROCYCLYL-4-MORPHOLIN-4-YLPYRIDINE-2-ONE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER AND DIABETES
  申请人：Sprint Bioscience AB

  公开号：US20210128571A1

  公开（公告）日：2021-05-06

  The invention provides novel 6-aryl or 6-heteroaryl 4-morpholin-4-yl-pyhdine-2-one compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, diabetes, inflammatory diseases, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R 1 , R 2 , R 3 and R 4 are as defined in the specification.
• 6-ARYL-4-MORPHOLIN-1-YLPYRIDONE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER AND DIABETES
  申请人：Sprint Bioscience AB

  公开号：US20220117974A1

  公开（公告）日：2022-04-21

  The invention provides novel 6-aryl or 6-heteroaryl 4-morpholin-4-yl-pyhdine-2-one compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, diabetes, inflammatory diseases, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R 1 , R 2 , R 3 and R 4 are as defined in the specification.