benzyl N-[1-(diphenoxyphosphoryl)butyl]carbamate | 130727-16-1

• 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: benzyl N-[1-(diphenoxyphosphoryl)butyl]carbamate
• 英文别名: Carbamic acid, [1-(diphenoxyphosphinyl)butyl]-, phenylmethyl ester；benzyl N-(1-diphenoxyphosphorylbutyl)carbamate
• CAS: 130727-16-1
• 化学式: C₂₄H₂₆NO₅P
• 分子量: 439.448
• InChiKey: UNYYGSNDHISNBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl N-[1-(diphenoxyphosphoryl)butyl]carbamate 在 氢溴酸 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 0.5h， 生成 N-[1-[oxido(diphenoxy)phosphaniumyl]butyl]formamide
  参考文献：
  名称：

  Synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters

  摘要：

  This letter describes the first example of the synthesis of isocyanide derivatives of alpha-aminoalkylphosphonate diphenyl esters. This method produces the title compounds in high purity and in very good yields. It also permits the generation of an alpha-aminophosphonate-based library of biologically active phosphonopeptides. Preliminary experiments demonstrate their application as substrates for the Ugi-type multicomponent condensation. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.04.058
• 作为产物：
  描述：

  苯酚 在 溶剂黄146 、 三氯化磷 作用下， 以 乙腈 为溶剂， 反应 8.0h， 生成 benzyl N-[1-(diphenoxyphosphoryl)butyl]carbamate
  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-activity analysis of peptidic Chlamydia HtrA inhibitors
  作者：Ayodeji A. Agbowuro、Jimin Hwang、Emma Peel、Rami Mazraani、Alexandra Springwald、James W. Marsh、Laura McCaughey、Allan B. Gamble、Wilhelmina M. Huston、Joel D.A. Tyndall

  DOI：10.1016/j.bmc.2019.07.049

  日期：2019.9

  Chlamydia trachomatis high temperature requirement A (CtHtrA) is a serine protease that performs proteolytic and chaperone functions in pathogenic Chlamydiae; and is seen as a prospective drug target. This study details the strategies employed in optimizing the irreversible CtHtrA inhibitor JO146 [Boc-Val-Pro-ValP(OPh)2] for potency and selectivity. A series of adaptations both at the warhead and specificity

  沙眼衣原体高温需要A（CtHtrA）是一种丝氨酸蛋白酶，在致病性衣原体中具有蛋白水解和伴侣功能。并被视为潜在的药物目标。这项研究详细介绍了针对效力和选择性优化不可逆CtHtrA抑制剂JO146 [Boc-Val-Pro-Val P（OPh）2 ]的策略。弹头和特异性残基P 1和P 3的一系列适应作用产生了23种类似物，已在人嗜中性弹性蛋白酶（HNE）和CtHtrA酶检测以及衣原体检测中进行了测试。细胞培养测定。还进行了胰蛋白酶和胰凝乳蛋白酶抑制试验以测量脱靶选择性。用α-酮基苯并噻唑代替膦酸酯部分可产生可逆的类似物，并具有相当大的CtHtrA抑制作用和细胞培养活性。在P 3（8a）处的叔亮氨酸对CtHtrA的抑制活性提高了约33倍， 对HNE的IC 50 = 0.68±0.02 µM，而在P 1处的缬氨酸保留了最佳的抗衣原体活性。这项研究提供了获得临床相关抑制剂的途径。
• Synthesis of Ursolic Phosphonate Derivatives as Potential Anti-HIV Agents
  作者：Sheng-Lou Deng、Isabelle Baglin、Mohammed Nour、Oxana Flekhter、Claudio Vita、Christian Cavé

  DOI：10.1080/10426500601088838

  日期：2007.3.15

  In order to search for new anti-tumor and anti-viral agents, a series of α-aminophosphonate conjugates of 3-O-β-acetyl ursolic acid were prepared. Their biological activities as cytotoxic and anti-HIV agents were evaluated. The preliminary bioassays indicate that synthesized compounds 7a–j have anti-HIV activity (targeting HIV-1 gp120 and CD4) and no cytotoxicity on HT-29 cells (human colon adenocarcinoma

  为了寻找新的抗肿瘤和抗病毒药物，制备了一系列 3-O-β-乙酰熊果酸的 α-氨基膦酸盐偶联物。评价了它们作为细胞毒性剂和抗HIV剂的生物活性。初步生物测定表明，合成的化合物 7a-j 具有抗 HIV 活性（靶向 HIV-1 gp120 和 CD4）并且对 HT-29 细胞（人结肠腺癌细胞系）没有细胞毒性。
• Remote Binding Energy in Antibody Catalysis:  Studies of a Catalytically Unoptimized Specificity Pocket
  作者：Herschel Wade、Thomas S. Scanlan

  DOI：10.1021/ja983017e

  日期：1999.2.1

  Binding interactions remote from the hydrolytic reaction center have been probed with substrate and phosphonate transition state analogues to understand how these types of interactions are used to promote catalysis in the 17E8 system, We find that the hapten-generated recogniton pocket in 17E8 has properties that are analogous to those of specificity pockets in enzymes, pie have also found that there are specific requirements to form catalytically productive interactions between the side chain and the recognition pocket including conformation, size, and geometry. An additional requirement includes Favorable simultaneous interactions between the side chain and binding packet along with favorable interactions with the oxyanion hole. The 17E8 side chain recognition pocket seems to be less catalytically efficient than analogous pockets in enzymatic systems. The apparent binding energy gained from the methylene-packet interactions in the 17E8 system is significantly smaller than those observed in natural enzymes. Furthermore, 17E8 does not use specific interactions in the recognition pocket to significantly affect catalytic turnover (k(cat)) which is thought to be a trait of an unoptimized catalyst. Analysis of the crystal structure of the 17E8,hapten complex has allowed for the identification of differences between the active sites of 17E8; and several proteases, The identified differences give insight to the sources of the inefficient use of binding energy.
• Toolbox of Fluorescent Probes for Parallel Imaging Reveals Uneven Location of Serine Proteases in Neutrophils
  作者：Paulina Kasperkiewicz、Yoav Altman、Maximiliano D’Angelo、Guy S. Salvesen、Marcin Drag

  DOI：10.1021/jacs.7b04394

  日期：2017.7.26

  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.
• Human Neutrophil Elastase Phosphonic Inhibitors with Improved Potency of Action
  作者：Łukasz Winiarski、Józef Oleksyszyn、Marcin Sieńczyk

  DOI：10.1021/jm300599x

  日期：2012.7.26

  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.