tert-butyl (3-oxo-3-(piperazin-1-yl)propyl)carbamate | 1052715-64-6

• 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: tert-butyl (3-oxo-3-(piperazin-1-yl)propyl)carbamate
• 英文别名: tert-butyl-[2-oxo-2-(1-piperazinyl)ethyl]carbamate；tert-butyl N-[3-oxo-3-(piperazin-1-yl)propyl]carbamate；tert-butyl N-(3-oxo-3-piperazin-1-ylpropyl)carbamate
• CAS: 1052715-64-6
• 化学式: C₁₂H₂₃N₃O₃
• mdl: MFCD18089561
• 分子量: 257.333
• InChiKey: JVJKTSYVPKDWMC-UHFFFAOYSA-N

物化性质

• 沸点：
  433.5±40.0 °C(Predicted)
• 密度：
  1.089±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (3-oxo-3-(piperazin-1-yl)propyl)carbamate 在 palladium on activated charcoal 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-[(S)-3-[4-(3-Amino-propionyl)-piperazin-1-yl]-2-(anthracene-2-sulfonylamino)-3-oxo-propyl]-benzamidine
  参考文献：
  名称：

  Secondary Amides of Sulfonylated 3-Amidinophenylalanine. New Potent and Selective Inhibitors of Matriptase

  摘要：

  Matriptase is an epithelium-derived type II transmembrane serine protease and has been implicated in the activation of substrates such as pro-HGF/SF and pro-uPA, which are likely involved in tumor progression and metastasis. Through screening, we have identified bis-basic secondary amides of sulfonylated 3-amidinophenylalanine as matriptase inhibitors. X-ray analyses of analogues 8 and 31 in complex with matriptase revealed that these inhibitors occupy, in addition to part of the previously described S4-binding site, the cleft formed by the molecular surface and the unique 60 loop of matriptase. Therefore, optimization of the inhibitors included the incorporation of appropriate sulfonyl substituents that could improve binding of these inhibitors into both characteristic matriptase subsites. The most potent derivatives inhibit matriptase highly selective with K(i) values below 5 nM. Molecular modeling revealed that their improved affinity results from interaction with the S4 site of matriptase. Analogues 8 and 59 were studied in an orthotopic xenograft mouse model of prostate cancer. Compared to control, both inhibitors reduced tumor growth, as well as tumor dissemination.

  DOI：

  10.1021/jm051272l
• 作为产物：
  描述：

  benzyl 4-(3-((tert-butoxycarbonyl)amino)propanoyl)piperazine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 以90%的产率得到tert-butyl (3-oxo-3-(piperazin-1-yl)propyl)carbamate
  参考文献：
  名称：

  一种连接体及制备方法和应用、基于沙利度胺的PROTACs的中间体及应用

  摘要：

  本发明属于有机化合物合成技术领域，尤其涉及一种连接体及制备方法和应用、基于沙利度胺的PROTACs的中间体及应用。本发明提供的双功能小分子PROTACs的连接体用于制备基于沙利度胺的双功能小分子PROTACs的中间体，所得中间体包括基于沙利度胺分子的结构和连接体基团结构，能够成功实现将沙利度胺与多种靶蛋白识别配体相连，为基于沙利度胺的双功能小分子PROTACs新药下一步的合成提供了便利。本发明提供的基于沙利度胺的PROTACs的中间体的制备方法，反应条件温和、合成简便高效。

  公开号：

  CN110845445A

文献信息

• PIM KINASE INHIBITORS AND METHODS OF THEIR USE
  申请人：Burger Matthew

  公开号：US20120208815A1

  公开（公告）日：2012-08-16

  New compounds, compositions and methods of inhibition of kinase activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one serine/threonine kinase or receptor tyrosine kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.

  提供了一种用于抑制人或动物主体中与肿瘤发生相关的激酶活性的新化合物、组合物和方法。在某些实施例中，这些化合物和组合物能够有效地抑制至少一种丝氨酸/苏氨酸激酶或受体酪氨酸激酶的活性。这些新的化合物和组合物可以单独使用或与至少一种额外的药物联合使用，用于治疗丝氨酸/苏氨酸激酶或受体酪氨酸激酶介导的疾病，如癌症。
• 10.1021/acs.jmedchem.4c00296
  作者：Gao, Yuan、Duan, Ji-Long、Wang, Chen-Chen、Yuan, Yinghui、Zhang, Pengpeng、Wang, Zong-Hao、Sun, Bowen、Zhou, Jiawei、Du, Xiaoli、Dang, Xiawen、Bai, Rui-Ting、Zhang, Hang、Xie, Tian、Ye, Xiang-Yang

  DOI：10.1021/acs.jmedchem.4c00296

  日期：——

  Bifunctional conjugates targeting PD-L1/PARP7 were designed, synthesized, and evaluated for the first time. Compounds B3 and C6 showed potent activity against PD-1/PD-L1 interaction (IC50 = 0.426 and 0.342 μM, respectively) and PARP7 (IC50 = 2.50 and 7.05 nM, respectively). They also displayed excellent binding affinity with hPD-L1, approximately 100–200-fold better than that of hPD-1. Both compounds

  首次设计、合成并评估了靶向 PD-L1/PARP7 的双功能缀合物。化合物B3和C6对 PD-1/PD-L1 相互作用（IC 50分别为 0.426 和 0.342 μM）和 PARP7（IC 50分别为 2.50 和 7.05 nM）表现出有效的活性。它们还表现出与 hPD-L1 优异的结合亲和力，比 hPD-1 强约 100-200 倍。这两种化合物都能恢复 T 细胞功能，导致 IFN-γ 分泌增加。在共培养测定中， B3和C6以浓度依赖性方式增强Jurkat T细胞对MDA-MB-231细胞的杀伤活性。此外， B3和C6在黑色素瘤B16-F10肿瘤小鼠模型中表现出显着的体内抗肿瘤功效，比BMS-1（一种PD-L1抑制剂）和RBN-2397（一种PARP7i临床候选药物）强5.3倍以上。剂量为25 mg/kg，没有观察到的副作用。这些结果为开发用于潜在抗癌治疗的双功能缀合物提供了宝贵的见解和理解。
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSES CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2006023400A3

  公开（公告）日：2006-06-08
• Discovery of O-(3-carbamimidoylphenyl)-l-serine amides as matriptase inhibitors using a fragment-linking approach
  作者：Rajeev Goswami、Gerd Wohlfahrt、Subhendu Mukherjee、Chakshusmathi Ghadiyaram、Jwala Nagaraj、Leena K. Satyam、Krishnaprasad Subbarao、Sreevalsam Gopinath、Narasimha R. Krishnamurthy、Hosahalli S. Subramanya、Murali Ramachandra

  DOI：10.1016/j.bmcl.2014.12.008

  日期：2015.2

  Matriptase is a cell-surface trypsin-like serine protease of epithelial origin, which cleaves and activates proteins including hepatocyte growth factor/scatter factor and proteases such as uPA, which are involved in the progression of various cancers. Here we report a fragment-linking approach, which led to the discovery of O-(3-carbamimidoylphenyl)-L-serine amides as potent matriptase inhibitors. The co-crystal structure of one of the potent inhibitors, 6 in complex with matriptase catalytic domain validated the working hypothesis guiding the development of this congeneric series and revealed the structural basis for matriptase inhibition. Replacement of a naphthyl group in 6 with 2,4,6-tri-isopropyl phenyl resulted in 10 with improved matriptase inhibition, which exhibited significant primary tumor growth inhibition in a mouse model of prostate cancer. Compounds such as 10, identified using a fragment-linking approach, can be explored further to understand the role of matriptase as a drug target in cancer and inflammation. (C) 2014 Elsevier Ltd. All rights reserved.
• US8822497B2
  申请人：——

  公开号：US8822497B2

  公开（公告）日：2014-09-02