Abu^p(OPh)₂*HBr | 1402801-31-3

• 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: Abu^p(OPh)₂*HBr
• 英文别名: 1-diphenoxyphosphorylpropan-1-amine;hydrobromide
• CAS: 1402801-31-3
• 化学式: BrH*C₁₅H₁₈NO₃P
• 分子量: 372.199
• InChiKey: FSCGDBTZTSFCMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.61
• 重原子数：
  21.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  61.55
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Abu^p(OPh)₂*HBr 在 2,4,6-三甲基吡啶 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.55h， 生成
  参考文献：
  名称：

  Toolbox of Fluorescent Probes for Parallel Imaging Reveals Uneven Location of Serine Proteases in Neutrophils

  摘要：

  Neutrophils, the front line defenders against infection, express four serine proteases (NSPs) that play roles in the control of cell-signaling pathways and defense against pathogens and whose imbalance leads to pathological conditions. Dissecting the roles of individual NSPs in humans is problematic because neutrophils are end-stage cells with a short half-life and minimal ongoing protein synthesis. To gain insight into the regulation of NSP activity we have generated a small-molecule chemical toolbox consisting of activity-based probes with different fluorophore-detecting groups with minimal wavelength overlap and highly selective natural and unnatural amino acid recognition sequences. The key feature of these activity-based probes is the ability to use them for simultaneous observation and detection of all four individual NSPs by fluorescence microscopy, a feature never achieved in previous studies. Using these probes we demonstrate uneven distribution of NSPs in neutrophil azurophil granules, such that they seem to be mutually excluded from each other, suggesting the existence of unknown granule-targeting mechanisms.

  DOI：

  10.1021/jacs.7b04394
• 作为产物：
  描述：

  苯酚 在 氢溴酸 、 溶剂黄146 、 三氯化磷 作用下， 以 乙腈 为溶剂， 反应 10.0h， 生成 Abu^p(OPh)₂*HBr
  参考文献：
  名称：

  Human Neutrophil Elastase Phosphonic Inhibitors with Improved Potency of Action

  摘要：

  Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of alpha-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a k(inact)/K-1 of 2353000 M-1 s(-1), which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.

  DOI：

  10.1021/jm300599x

文献信息

• Structure-based design, synthesis, and evaluation of the biological activity of novel phosphoroorganic small molecule IAP antagonists
  作者：Agnieszka Łupicka-Słowik、Mateusz Psurski、Renata Grzywa、Monika Cuprych、Jarosław Ciekot、Waldemar Goldeman、Elżbieta Wojaczyńska、Jacek Wojaczyński、Józef Oleksyszyn、Marcin Sieńczyk

  DOI：10.1007/s10637-020-00923-4

  日期：2020.10

  caspases (Smac) that share an IAP binding motif (IBM). The main purpose of the present study was the design and synthesis of phosphorus-based peptidyl antagonists of IAPs that mimic the endogenous Smac protein, which blocks the interaction between IAPs and caspases. Based on the structure of the IAP antagonist and recently reported thiadiazole derivatives, we designed and evaluated the biochemical properties

  新型抗癌疗法采用的策略之一是通过阻断细胞凋亡蛋白抑制剂 (IAP) 和半胱天冬酶之间的相互作用，使细胞凋亡过程回到正轨。半胱天冬酶的活性受半胱天冬酶/半胱天冬酶原蛋白水解级联中的半胱天冬酶本身以及它们与 IAP 的相互作用调节。半胱天冬酶可以从 IAP 的抑制影响中释放出来，这些蛋白质是共享一个 IAP 结合基序 (IBM) 的促凋亡蛋白，例如半胱天冬酶的次级线粒体激活剂 (Smac)。本研究的主要目的是设计和合成 IAP 的磷基肽基拮抗剂，模拟内源性 Smac 蛋白，阻断 IAP 和半胱天冬酶之间的相互作用。基于 IAP 拮抗剂的结构和最近报道的噻二唑衍生物，N -Me-Ala-Val/Chg-Pro-OH 基序（Chg：环己基甘氨酸）。获得的化合物与凋亡蛋白重复序列​​杆状病毒抑制剂 X-连锁抑制剂（XIAP BIR3）结构域的结合沟相互作用的能力通过荧光偏振测定进行检查，同时它们诱导自身泛素化随后蛋白酶体降解的潜力使用
• NOVEL ACTIVITY-BASED PROBES FOR NEUTROPHIL ELASTASE AND THEIR USE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20220050107A1

  公开（公告）日：2022-02-17

  The present invention relates to compounds of formula I, wherein D is a detectable moiety, or salts thereof, which can be used as activity-based probes for neutrophil elastase, as well as to methods for detecting neutrophil elastase (NE) activity in a tissue sample lysate, and related diagnostic methods using compounds of formula I.