(S)-tert-butyl 2-(propylcarbamoyl)pyrrolidine-1-carboxylate | 876064-45-8

• 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: (S)-tert-butyl 2-(propylcarbamoyl)pyrrolidine-1-carboxylate
• 英文别名: tert-Butyl (S)-2-(propylcarbamoyl)pyrrolidine-1-carboxylate；tert-butyl (2S)-2-(propylcarbamoyl)pyrrolidine-1-carboxylate
• CAS: 876064-45-8
• 化学式: C₁₃H₂₄N₂O₃
• 分子量: 256.345
• InChiKey: YZYTZIMLRBYZMH-JTQLQIEISA-N

物化性质

• 沸点：
  406.2±34.0 °C(Predicted)
• 密度：
  1.067±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 2-(propylcarbamoyl)pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以86%的产率得到pyrrolidine-2-carboxylic acid propylamide
  参考文献：
  名称：

  具有扩展的聚集体和凝胶的超分子催化：自组装引起的立体选择性反演

  摘要：

  在甲苯中自组装的L-脯氨酸-L-缬氨酸二肽衍生物已被研究为将环己酮共轭添加到反-β-硝基苯乙烯中的立体选择性催化剂。观察到与催化剂的聚集有关的对立体选择性的显着影响。观察到在甲苯中形成超分子凝胶的化合物1和不是胶凝剂的化合物2的催化活性之间存在显着差异。在前一种情况下，反应的对映选择性几乎对催化剂浓度和温度的变化不敏感，但在化合物2的情况下，催化活性受这些变量的影响很大。结构研究表明，可以通过考虑与聚集过程相关的催化L-脯氨酸衍生物经历的显着构象变化，使结果合理化。结果表明，催化剂的自组装是有机催化反应的立体选择结果中要考虑的一个非常重要的问题。特别相关的事实是，超分子凝胶用作有机催化剂的出现是一种在不同条件下提供可靠和恒定的立体选择性并易于回收的附加值的技术。

  DOI：

  10.1002/chem.201000654
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 碳酸氢钠 、 二乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 (S)-tert-butyl 2-(propylcarbamoyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  α-Substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents

  摘要：

  We report the synthesis and biological activity of analogues of VRC3375 (N-hydroxy-3-R-butyl-3-[(2-S-(tert-butoxycarbonyl)-pyrrolidin-1-ylcarbonyl]propionamide), an orally active peptide deformylase inhibitor. This study explores the structureactivity relationship of various chelator groups, alpha substituents, P-2' and P-3' substituents in order to achieve optimal antibacterial activity with minimal toxicity liability. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.07.020

文献信息

• Structural Optimizations of Thieno[3,2-<i>b</i>]pyrrole Derivatives for the Development of Metabolically Stable Inhibitors of Chikungunya Virus
  作者：Kuan-Chieh Ching、Thi Ngoc Quy Tran、Siti Naqiah Amrun、Yiu-Wing Kam、Lisa F. P. Ng、Christina L. L. Chai

  DOI：10.1021/acs.jmedchem.7b00180

  日期：2017.4.13

  discovery of thieno[3,2-b]pyrrole 1b that displayed good antiviral activity against CHIKV infection in vitro. However, it has a short half-life in the presence of human liver microsomes (HLMs) (T1/2 = 2.91 min). Herein, we report further optimization studies in which potential metabolically labile sites on compound 1b were removed or modified, resulting in the identification of thieno[3,2-b]pyrrole 20 and

  Chikungunya病毒（CHIKV）是一种重新出现的载体传播的alpha病毒，目前尚无针对CHIKV的经过批准的有效抗病毒治疗。我们先前报道了噻吩并[3,2- b ]吡咯1b的发现，它在体外对CHIKV感染表现出良好的抗病毒活性。但是，它在人肝微粒体（HLM）存在下的半衰期很短（T 1/2 = 2.91分钟）。本文中，我们报告了进一步的优化研究，其中化合物1b上潜在的代谢不稳定位点被去除或修饰，从而鉴定了噻吩并[3,2- b ]吡咯20和吡咯并[2,3- d ]噻唑23c在HLM中具有高达17倍的代谢半衰期增加，并具有良好的体内药代动力学特性。化合物20不仅减缓了病毒RNA的产生，并显示出对其他α病毒和CHIKV分离株的广谱抗病毒活性，而且还显示出有限的细胞毒性作用（CC 50 > 100μM）。这些研究已经确定了两种化合物，它们有可能作为抗CHIKV感染的抗病毒药物进行进一步开发。
• Compounds Binding to the S2−S3 Pockets of Thrombin
  作者：Mikael Nilsson、Markku Hämäläinen、Maria Ivarsson、Johan Gottfries、Yafeng Xue、Sebastian Hansson、Roland Isaksson、Tomas Fex

  DOI：10.1021/jm8011849

  日期：2009.5.14

  A set of compounds designed to bind to the S2-S3 pockets of thrombin was prepared. These compounds included examples with no interactions in the S1 pocket. Proline, a common P2 in many thrombin inhibitors, was combined with known P3 residues and P1 substituents of varying size and lipophilicity. Binding constants were determined using surface plasmon resonance (SPR) biosensor technology and were found to be in good agreement with results from an enzyme assay. A dramatic increase in affinity (100-1000 times) was seen for compounds incorporating an amino group capable of forming a hydrogen bond with gly216 in the protein backbone. The ligand efficiency was increased by including substituents that form stronger hydrophobic interactions with the P1 pocket. The binding mode was confirmed by X-ray analysis, which revealed the anticipated binding motif that included hydrogen bonds as well as a tightly bound water molecule. A QSAR model indicated that hydrogen bonding and lipophilicity were important for the prediction of binding constants. The results described here may have implications for how directed compound libraries for shallow protein pockets, like S2 and S3 in serine proteases, can be designed.
• AMINO-PYRAZINECARBOXAMIDE COMPOUNDS, CONJUGATES, AND USES THEREOF
  申请人：Silverback Therapeutics, Inc.

  公开号：US20220362396A1

  公开（公告）日：2022-11-17

  Amino-pyrazinecarboxamide compounds, conjugates, and pharmaceutical compositions for use in the treatment of disease, such as cancer, are disclosed herein. The disclosed compounds are useful, among other things, in the treating of cancer and fibrosis and modulating TGFβR2. Additionally, compounds incorporated into a conjugate with an antibody construct are described herein.
• α-Substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents
  作者：R. Jain、A. Sundram、S. Lopez、G. Neckermann、C. Wu、C. Hackbarth、D. Chen、W. Wang、N.S. Ryder、B. Weidmann、D. Patel、J. Trias、R. White、Z. Yuan

  DOI：10.1016/j.bmcl.2003.07.020

  日期：2003.12

  We report the synthesis and biological activity of analogues of VRC3375 (N-hydroxy-3-R-butyl-3-[(2-S-(tert-butoxycarbonyl)-pyrrolidin-1-ylcarbonyl]propionamide), an orally active peptide deformylase inhibitor. This study explores the structureactivity relationship of various chelator groups, alpha substituents, P-2' and P-3' substituents in order to achieve optimal antibacterial activity with minimal toxicity liability. (C) 2003 Elsevier Ltd. All rights reserved.
• Supramolecular Catalysis with Extended Aggregates and Gels: Inversion of Stereoselectivity Caused by Self-Assembly
  作者：Francisco Rodríguez-Llansola、Juan F. Miravet、Beatriu Escuder

  DOI：10.1002/chem.201000654

  日期：——

  self‐assemble in toluene, have been studied as stereoselective catalysts in the conjugate addition of cyclohexanone to trans‐β‐nitrostyrene. Remarkable effects on the stereoselectivity are observed associated to the aggregation of the catalyst. Outstanding differences were observed between the catalytic activity of compound 1, which forms supramolecular gels in toluene, and compound 2, which is not a gelator

  在甲苯中自组装的L-脯氨酸-L-缬氨酸二肽衍生物已被研究为将环己酮共轭添加到反-β-硝基苯乙烯中的立体选择性催化剂。观察到与催化剂的聚集有关的对立体选择性的显着影响。观察到在甲苯中形成超分子凝胶的化合物1和不是胶凝剂的化合物2的催化活性之间存在显着差异。在前一种情况下，反应的对映选择性几乎对催化剂浓度和温度的变化不敏感，但在化合物2的情况下，催化活性受这些变量的影响很大。结构研究表明，可以通过考虑与聚集过程相关的催化L-脯氨酸衍生物经历的显着构象变化，使结果合理化。结果表明，催化剂的自组装是有机催化反应的立体选择结果中要考虑的一个非常重要的问题。特别相关的事实是，超分子凝胶用作有机催化剂的出现是一种在不同条件下提供可靠和恒定的立体选择性并易于回收的附加值的技术。