(1-Benzyloxycarbonylamino-propyl)-phosphonic acid diphenyl ester | 65164-81-0

• 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: (1-Benzyloxycarbonylamino-propyl)-phosphonic acid diphenyl ester
• 英文别名: Benzyl 1-(Diphenoxyphosphoryl)Propylcarbamate；benzyl N-(1-diphenoxyphosphorylpropyl)carbamate
• CAS: 65164-81-0
• 化学式: C₂₃H₂₄NO₅P
• 分子量: 425.421
• InChiKey: VMMMBCJXTBUYKN-UHFFFAOYSA-N

物化性质

• 沸点：
  568.1±50.0 °C(Predicted)
• 密度：
  1.231±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  (1-Benzyloxycarbonylamino-propyl)-phosphonic acid diphenyl ester 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 生成 Abu^p(OPh)₂*HBr
  参考文献：
  名称：

  基于结构的新型磷酸有机小分子 IAP 拮抗剂生物活性的设计、合成和评估。

  摘要：

  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

  DOI：

  10.1007/s10637-020-00923-4
• 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 (1-Benzyloxycarbonylamino-propyl)-phosphonic acid diphenyl ester
  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

• SYNTHESIS OF O,O-DIPHENYL [SUBSTITUTED (2-SELENOMORPHOLIN-4-YL-ACETYL AMINO)] ALKYL PHOSPHONATES
  作者：Liming Hu、Zhiyuan Chen、Shengmei Lu、Xueshu Li、Zhaojie Liu、Hansheng Xu

  DOI：10.1080/10426500490459687

  日期：2004.6

  A series of O,O-diphenyl [substituted (2-selenomorpholin-4-yl-acetyl amino)] alkyl phosphonates were synthesized by the reactions of selenomorpholine with O,O-diphenyl 2-chloro- acetylamino alkyl phosphonates. The structures of all new compounds have been confirmed by H-1 NMR, P-31 NMR, IR spectroscopy, Mass spectroscopy and elemental analyses.
• 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.
• Peptide deformylase activated prodrugs
  申请人：Ballatore Carlo

  公开号：US20060063743A1

  公开（公告）日：2006-03-23

  This invention provides compounds and methods for using them to inhibit the growth of microorganism that expresses Peptide Deformylase, the compounds having the general formula:
• US7001922B2
  申请人：——

  公开号：US7001922B2

  公开（公告）日：2006-02-21