tert-butyl (S)-(5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)carbamate | 216656-55-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (S)-(5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)carbamate
• CAS: 216656-55-2
• 化学式: C₂₂H₂₇NO₄S
• 分子量: 401.527
• InChiKey: AVUFAGOWJIRYNJ-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  72.47
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)carbamate 在 1-丙基磷酸酐 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.17h， 生成 4-Methyl-piperazine-1-carboxylic acid [(S)-1-((E)-(S)-3-benzenesulfonyl-1-phenethyl-allylcarbamoyl)-2-phenyl-ethyl]-amide
  参考文献：
  名称：

  [EN] INHIBITORS OF SARS COV-2 INFECTION AND USES THEREOF
  [FR] INHIBITEURS D'INFECTION À SARS-COV-2 ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2022047054A3
• 作为产物：
  描述：

  Boc-L-高苯丙氨酸 在 lithium aluminium tetrahydride 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.33h， 生成 tert-butyl (S)-(5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)carbamate
  参考文献：
  名称：

  [EN] INHIBITORS OF SARS COV-2 INFECTION AND USES THEREOF
  [FR] INHIBITEURS D'INFECTION À SARS-COV-2 ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2022047054A3

文献信息

• Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study
  作者：Patrick Müller、Mergim Meta、Jan Laurenz Meidner、Marvin Schwickert、Jessica Meyr、Kevin Schwickert、Christian Kersten、Collin Zimmer、Stefan Josef Hammerschmidt、Ariane Frey、Albin Lahu、Sergio de la Hoz-Rodríguez、Laura Agost-Beltrán、Santiago Rodríguez、Kira Diemer、Wilhelm Neumann、Florenci V. Gonzàlez、Bernd Engels、Tanja Schirmeister

  DOI：10.3390/ijms24087226

  日期：——

  Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding. Therefore, the right combination of a reactive warhead with a well-suited peptidomimetic sequence is of great importance. Herein, the selectivities of well-known warheads combined with peptidomimetic sequences suited for five different proteases were investigated, highlighting the impact of both structure parts (warhead and peptidomimetic sequence) for affinity and selectivity. Molecular docking gave insights into the predicted binding modes of the inhibitors inside the binding pockets of the different enzymes. Moreover, the warheads were investigated by NMR and LC-MS reactivity assays against serine/threonine and cysteine nucleophile models, as well as by quantum mechanics simulations.

  近年来，共价拟肽蛋白酶抑制剂在药物研发中备受关注。这些抑制剂通过被称为弹头的亲电基团与具有催化活性的氨基酸共价结合。共价抑制在药效学特性方面具有优势，但也可能因非选择性脱靶蛋白结合而产生毒性风险。因此，将活性弹头与合适的拟肽序列正确地结合在一起非常重要。本文研究了知名弹头与适合五种不同蛋白酶的拟肽序列相结合的选择性，强调了两个结构部分（弹头和拟肽序列）对亲和力和选择性的影响。分子对接深入了解了抑制剂在不同酶的结合口袋内的预测结合模式。此外，还通过核磁共振和液相色谱-质谱反应性测定以及量子力学模拟，研究了弹头与丝氨酸/苏氨酸和半胱氨酸亲核模型的反应性。
• Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition
  作者：Rita Capela、Rudi Oliveira、Lídia M. Gonçalves、Ana Domingos、Jiri Gut、Philip J. Rosenthal、Francisca Lopes、Rui Moreira

  DOI：10.1016/j.bmcl.2009.04.100

  日期：2009.6

  A series of artemisinin-vinyl sulfone hybrid molecules with the potential to act in the parasite food vacuole via endoperoxide activation and falcipain inhibition was synthesized and screened for antiplasmodial activity and falcipain-2 inhibition. All conjugates were active against the Plasmodium falciparum W2 strain in the low nanomolar range and those containing the Leu-hPhe core inhibited falcipain-2 in low micromolar range. (C) 2009 Elsevier Ltd. All rights reserved.