7-苄基-1,3,7-三氮杂螺[4.4]-2,4-壬二酮 | 28863-87-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: 7-苄基-1,3,7-三氮杂螺[4.4]-2,4-壬二酮
• 英文名称: 7-benzyl-1,3,7-triazaspiro[4.4]nonane-2,4-dione
• 英文别名: 7-benzyl-1,3,7-triaza-spiro[4.4]nonane-2,4-dione
• CAS: 28863-87-8
• 化学式: C₁₃H₁₅N₃O₂
• mdl: MFCD13196848
• 分子量: 245.281
• InChiKey: RZHBDUGHJGKVFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20°C，干燥

反应信息

• 作为反应物：
  描述：

  7-苄基-1,3,7-三氮杂螺[4.4]-2,4-壬二酮 在 盐酸 、 氢溴酸 、 溶剂黄146 作用下， 反应 96.0h， 以73%的产率得到1-苄基-3-氨基吡咯烷-3-甲酸
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 1

  摘要：

  In an attempt to search for clinically useful antitumor agents, we have discovered that a series of 1,1-disubstituted-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids possessed moderate cytotoxic activity.,We investigated the structure-activity relationships in this series of compounds by changing N-1 and C-7 positions and the core ring structure itself and evaluated the synthesized compounds against several murine and human tumor cell lines. These modifications led us to the following findings. (1) The 2-thiazolyl group at the N-1 position of the naphthyridine structure is the best substituent for antitumor activity. (2) Regarding core ring structure, the naphthyridine derivative is the most active followed by pyridopyrimidine analogue. (3) At the C-7 position, -aminopyrrolidine derivatives are more effective than other amines or thioether derivatives. Finally, the trans-3-amino-4-methoxypyrrolidinyl derivative (43j), and the 3-amino-3-methylpyrrolidinyl derivative (43f) as well as 3-aminopyrrolidinyl derivative (AT-3639, 1) were determined to be effective in in vitro and in vivo antitumor assays, and their activity was comparable to that of etoposide.

  DOI：

  10.1021/jm010057b
• 作为产物：
  描述：

  碳酸氢铵 、 potassium cyanide 、 1-苄基-3-吡咯烷酮 以 甲醇 、 水 为溶剂， 反应 0.17h， 以50%的产率得到7-苄基-1,3,7-三氮杂螺[4.4]-2,4-壬二酮
  参考文献：
  名称：

  微波辅助合成功能化螺乙内酰脲的3D优先片段，用于侦察化学空间

  摘要：

  基于片段的药物设计已成功应用于大量蛋白质，但是，为了将这一概念扩展到最苛刻的目标，例如蛋白质与蛋白质的相互作用，需要使用新的和原始的3D特权丰富当前的片段库碎片。我们的目标是开发微波辅助快速合成27个新的螺乙内酰脲片段的方法。其中24种化合物显示出高水溶性。这些分子是根据其最小化构象异构体的归一化主要惯性矩绘制的，并且大多数化合物都倾向于占据三角形图中人口不足的区域。最后，我们证明了乙内酰脲环可以选择性地为N-单烷基化提供了快速官能化的进一步途径。

  DOI：

  10.1016/j.tetlet.2016.05.065

文献信息

• 8-METHOXYQUINOLONECARBOXYLIC ACID DERIVATIVE
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0677522A1

  公开（公告）日：1995-10-18

  An 8-methoxyquinolonecarboxylic acid derivative represented by general formula (I), and optical isomers, pharmaceutically acceptable salts and hydrates thereof, wherein R₁ represents hydrogen, lower alkyl, phenylalkyl or an in vivo hydrolyzable ester residue; R₂ represents hydrogen or methyl; and n represents an integer of 0 or 1. This derivative has a wide antimicrobial spectrum based on the activity potentiated in vitro and in vivo against gram-positive bacteria while retaining the potent antibacterial activity of the conventional quinolonecarboxylate bactericides against gram-negative bacteria. Since it scarcely has problematic side effects and is reduced in toxicity, it is promising as a bactericide having more excellent clinical effects.

  通式(I)代表的 8-甲氧基喹啉羧酸衍生物及其光学异构体、药学上可接受的盐和水合物，其中 R₁ 代表氢、低级烷基、苯基烷基或体内可水解的酯残基；R₂ 代表氢或甲基；n 代表 0 或 1 的整数。根据体外和体内对革兰氏阳性菌的增效活性，这种衍生物具有广泛的抗菌谱，同时保留了传统喹啉羧酸盐杀菌剂对革兰氏阴性菌的强效抗菌活性。由于它几乎没有副作用，毒性也较低，因此有望成为一种临床效果更佳的杀菌剂。
• SPIROCYCLIC COMPOUNDS
  申请人：C4 Therapeutics, Inc.

  公开号：US20210070763A1

  公开（公告）日：2021-03-11

  The present invention provides compounds and intermediates. The present invention also provides compounds which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and their use for the treatment of abnormal cellular proliferation. The present invention also provides compounds that may be used as synthetic intermediates in the synthesis of bifunctional compounds used for targeted protein degradation.
• Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 1
  作者：Kyoji Tomita、Yasunori Tsuzuki、Koh-ichiro Shibamori、Masanori Tashima、Fumie Kajikawa、Yuji Sato、Shigeki Kashimoto、Katsumi Chiba、Katsuhiko Hino

  DOI：10.1021/jm010057b

  日期：2002.12.1

  In an attempt to search for clinically useful antitumor agents, we have discovered that a series of 1,1-disubstituted-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids possessed moderate cytotoxic activity.,We investigated the structure-activity relationships in this series of compounds by changing N-1 and C-7 positions and the core ring structure itself and evaluated the synthesized compounds against several murine and human tumor cell lines. These modifications led us to the following findings. (1) The 2-thiazolyl group at the N-1 position of the naphthyridine structure is the best substituent for antitumor activity. (2) Regarding core ring structure, the naphthyridine derivative is the most active followed by pyridopyrimidine analogue. (3) At the C-7 position, -aminopyrrolidine derivatives are more effective than other amines or thioether derivatives. Finally, the trans-3-amino-4-methoxypyrrolidinyl derivative (43j), and the 3-amino-3-methylpyrrolidinyl derivative (43f) as well as 3-aminopyrrolidinyl derivative (AT-3639, 1) were determined to be effective in in vitro and in vivo antitumor assays, and their activity was comparable to that of etoposide.
• Microwave-assisted synthesis of functionalized spirohydantoins as 3-D privileged fragments for scouting the chemical space
  作者：Hugues Prevet、Marion Flipo、Pascal Roussel、Benoit Deprez、Nicolas Willand

  DOI：10.1016/j.tetlet.2016.05.065

  日期：2016.6

  protein–protein interactions, it is required to enrich current fragment libraries with new and original 3D privileged fragments. Our goal was to develop a rapid microwave-assisted synthesis of 27 new privileged spirohydantoin fragments. Among them 24 compounds showed a high water solubility. These molecules were plotted according to the normalized principal moments of inertia of their minimized conformers

  基于片段的药物设计已成功应用于大量蛋白质，但是，为了将这一概念扩展到最苛刻的目标，例如蛋白质与蛋白质的相互作用，需要使用新的和原始的3D特权丰富当前的片段库碎片。我们的目标是开发微波辅助快速合成27个新的螺乙内酰脲片段的方法。其中24种化合物显示出高水溶性。这些分子是根据其最小化构象异构体的归一化主要惯性矩绘制的，并且大多数化合物都倾向于占据三角形图中人口不足的区域。最后，我们证明了乙内酰脲环可以选择性地为N-单烷基化提供了快速官能化的进一步途径。