哌嗪-1-基-噻吩-3-基-甲酮 | 59939-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 哌嗪-1-基-噻吩-3-基-甲酮
• 英文名称: (piperazin-1-yl)(thiophen-3-yl)methanone
• 英文别名: 1-(3-Thienoyl)-piperazin；1-(thiophene-3-carbonyl)-piperazine；Piperazin-1-yl(thiophen-3-yl)methanone
• CAS: 59939-74-1
• 化学式: C₉H₁₂N₂OS
• mdl: MFCD08444712
• 分子量: 196.273
• InChiKey: GOTAZYHBTVLKFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  60.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-[(4-oxo-3H-phthalazin-1-yl)methyl]thiophene-3-carboxylic acid 、 哌嗪-1-基-噻吩-3-基-甲酮 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 水 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 49.0h， 生成 4-[[4-[4-(thiophene-3-carbonyl)piperazine-1-carbonyl]thiophen-2-yl]methyl]-2H-phthalazin-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors

  摘要：

  We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation.

  DOI：

  10.1016/j.bmcl.2014.07.001
• 作为产物：
  描述：

  tert-Butyl 4-(thiophene-3-carbonyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 哌嗪-1-基-噻吩-3-基-甲酮
  参考文献：
  名称：

  Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors

  摘要：

  We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation.

  DOI：

  10.1016/j.bmcl.2014.07.001

文献信息

• Efficient monoacylation of symmetrical secondary alkanediamines and synthesis of unsymmetrical diacylated alkanediamines. A new L-proline-based organocatalyst
  作者：Laure Moulat、Jean Martinez、Xavier J. Salom-Roig

  DOI：10.24820/ark.5550190.p011.054

  日期：——

  developed for the monoacylation of several unprotected alkanediamines with carboxylic acids by using PyBOP-HOBt as coupling agent in the presence of DIEA at room temperature. Yields were moderate with primary alkanediamines and good to excellent with linear or cyclic secondary ones. To illustrate the utility of these monoacylated products, six unsymmetrical diacylated alkanediamines were synthesized

  通过使用 PyBOP-HOBt 作为偶联剂，在室温下，在 DIEA 的存在下，开发了一种简单的程序，用于将几种未保护的链烷二胺与羧酸进行单酰化。伯链烷二胺的产率适中，直链或环状仲胺的产率从好到极好。为了说明这些单酰化产物的效用，合成了六种不对称的二酰化链烷二胺。此外，这些化合物之一被评估为不对称羟醛反应中的有机催化剂。
• Discovery of proteolysis-targeting chimera targeting undruggable proteins using a covalent ligand screening approach
  作者：Hyeonjun Lee、Ju Yeon Lee、Hyunsoo Jang、Hye Young Cho、Minhee Kang、Sang Hyun Bae、Suin Kim、Eunji Kim、Jaebong Jang、Jin Young Kim、Young Ho Jeon

  DOI：10.1016/j.ejmech.2023.115929

  日期：2024.1

  Targeted protein degradation (TPD) technology, such as proteolysis-targeting chimera (PROTAC), has become a new therapeutic modality. However, the degradation of undruggable proteins, such as those involved in protein-protein interactions (PPIs), using PROTAC is still limited owing to the difficulties in finding small-molecule binders of these proteins. To identify new chemical moieties that bind to

  靶向蛋白降解（TPD）技术，例如蛋白水解靶向嵌合体（PROTAC），已成为一种新的治疗方式。然而，由于难以找到这些蛋白质的小分子结合物，使用 PROTAC 降解不可成药的蛋白质，例如那些参与蛋白质-蛋白质相互作用 (PPI) 的蛋白质，仍然受到限制。为了识别与目标蛋白 (POI) 靶位点结合的新化学部分，我们使用液相色谱-串联质谱 (LC-MS/MS) 进行了位点特异性和基于片段的共价配体筛选。为了将选定的命中应用于 PROTAC 方法，进行了二维 (2D) 核磁共振 (NMR) 实验，以评估其类似物在没有共价弹头的情况下的可逆结合。为了证明所提出的方法，选择人鼠双分钟 (MDM)2 作为模型系统，因为它涉及 PPI 并且已知是可降解的靶蛋白。蛋白质印迹分析表明，新合成的 PROTAC 掺入了筛选命中的可逆类似物，以剂量和时间依赖性方式影响降解。这种方法使得使用 PROTAC 技术来开发以前不可成药的蛋白质来治疗
• Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors
  作者：Ling-xiao Wang、Xin-bo Zhou、Meng-liang Xiao、Ning Jiang、Feng Liu、Wen-xia Zhou、Xiao-kui Wang、Zhi-bing Zheng、Song Li

  DOI：10.1016/j.bmcl.2014.07.001

  日期：2014.8

  We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation.