(5-oxo-5H-1,6-naphthyridin-6-yl)acetic acid ethyl ester | 1173699-51-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (5-oxo-5H-1,6-naphthyridin-6-yl)acetic acid ethyl ester
• 英文别名: ethyl 2-(5-oxo-1,6-naphthyridin-6(5H)-yl)acetate；ethyl 2-(5-oxo-1,6-naphthyridin-6-yl)acetate
• CAS: 1173699-51-8
• 化学式: C₁₂H₁₂N₂O₃
• 分子量: 232.239
• InChiKey: VNJAZLGAGCBSGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5-oxo-5H-1,6-naphthyridin-6-yl)acetic acid ethyl ester 在 lithium hydroxide 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以90%的产率得到(5-oxo-5H-1,6-naphthyridin-6-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：

  1,6-萘并吡啶-5(6H)-酮 、 溴乙酸乙酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以60%的产率得到(5-oxo-5H-1,6-naphthyridin-6-yl)acetic acid ethyl ester
  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

• Fused heterocyclic derivatives and methods of use
  申请人：Albrecht Brian K.

  公开号：US20090318436A1

  公开（公告）日：2009-12-24

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗疾病，例如HGF介导的疾病具有有效性。该发明包括新颖的化合物、类似物、前药和其药学上可接受的盐，以及预防和治疗涉及癌症等疾病和其他不适或状况的药物组合物和方法。该发明还涉及制备这种化合物的过程，以及在这种过程中有用的中间体。
• FUSED HETEROCYCLIC DERIVATIVES AND METHODS OF USE
  申请人：Albrecht Brian K.

  公开号：US20120107275A1

  公开（公告）日：2012-05-03

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物可用于预防和治疗疾病，如HGF介导的疾病。本发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的盐、药物组合物以及预防和治疗涉及癌症等疾病和其他不适或病况的方法。本发明还涉及制备这种化合物的方法，以及在这些过程中有用的中间体。
• 6-([1,2,4]TRIAZOLO[4,3-A]PYRIDIN-3-YLMETHYL)-1,6-NAPHTHYRIDIN-5(6H)-ONE DERIVATIVES AS C-MET INHIBITORS
  申请人：Amgen Inc.

  公开号：EP2231663B1

  公开（公告）日：2017-08-02
• A 6-([1,2,4]TRIAZOLO[4,3-A]PYRIDIN-3-YLMETHYL)-1,6-NAPHTHYRIDIN-5(6H)-ONE DERIVATIVE AS C-MET INHIBITOR
  申请人：Amgen, Inc

  公开号：EP3170824B1

  公开（公告）日：2020-07-01
• US8198448B2
  申请人：——

  公开号：US8198448B2

  公开（公告）日：2012-06-12