benzyl N-[4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-1-diphenoxyphosphorylbutyl]carbamate | 695171-98-3

• 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: benzyl N-[4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-1-diphenoxyphosphorylbutyl]carbamate
• CAS: 695171-98-3
• 化学式: C₃₅H₄₅N₄O₉P
• 分子量: 696.737
• InChiKey: HBMBIPBRBVRDAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  49
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  163
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  benzyl N-[4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-1-diphenoxyphosphorylbutyl]carbamate 在 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成
  参考文献：
  名称：

  Phosphonate inhibitors of West Nile virus NS2B/NS3 protease

  摘要：

  West Nile virus (WNV) is a member of the flavivirus genus belonging to the Flaviviridae family. The viral serine protease NS2B/NS3 has been considered an attractive target for the development of anti-WNV agents. Although several NS2B/NS3 protease inhibitors have been described so far, most of them are reversible inhibitors. Herein, we present a series of alpha-aminoalkylphosphonate diphenyl esters and their peptidyl derivatives as potent inhibitors of the NS2B/NS3 protease. The most potent inhibitor identified was Cbz-Lys-Arg-(4-GuPhe)(P)(OPh)(2) displaying K-i and k(2)/K-i values of 0.4 mu M and 28 265 M(-1)s(-1), respectively, with no significant inhibition of trypsin, cathepsin G, and HAT protease.

  DOI：

  10.1080/14756366.2018.1506772
• 作为产物：
  描述：

  氨基甲酸苄酯 在 copper(II) bis(trifluoromethanesulfonate) 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 benzyl N-[4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-1-diphenoxyphosphorylbutyl]carbamate
  参考文献：
  名称：

  The first potent diphenyl phosphonate KLK4 inhibitors with unexpected binding kinetics

  摘要：

  我们报告了第一批高效、选择性的小分子KLK4抑制剂，显示出令人惊讶的可逆结合动力学。

  DOI：

  10.1039/c5md00288e

文献信息

• Compounds and methods for protease detection
  申请人：Martin Stella Lorraine

  公开号：US09340820B2

  公开（公告）日：2016-05-17

  Alternative methods for the detection and measurement of proteases in biological samples and compounds which allow for such detection are required to allow for rapid and selective identification of these enzymes. Compounds which allow for selective identification of these enzymes are provided with assays and kits for their use.

  需要提供用于生物样本中蛋白酶检测和测量的替代方法和允许进行快速和选择性酶识别的化合物，以便提供这些酶的快速和选择性识别。提供了允许对这些酶进行选择性识别的化合物，并提供了用于其使用的检测和试剂盒。
• Parallel imaging of coagulation pathway proteases activated protein C, thrombin, and factor Xa in human plasma
  作者：Sylwia Modrzycka、Sonia Kołt、Stéphanie G. I. Polderdijk、Ty E. Adams、Stanisław Potoczek、James A. Huntington、Paulina Kasperkiewicz、Marcin Drąg

  DOI：10.1039/d2sc01108e

  日期：——

  Activated protein C (APC), thrombin, and factor (f) Xa are vitamin K-dependent serine proteases that are key factors in blood coagulation. Moreover, they play important roles in inflammation, apoptosis, fibrosis, angiogenesis, and viral infections. Abnormal activity of these coagulation factors has been related to multiple conditions, such as bleeding and thrombosis, Alzheimer's disease, sepsis, multiple

  活化蛋白 C (APC)、凝血酶和因子 (f) Xa 是维生素 K 依赖性丝氨酸蛋白酶，它们是血液凝固的关键因素。此外，它们在炎症、细胞凋亡、纤维化、血管生成和病毒感染中发挥重要作用。这些凝血因子的异常活动与多种疾病有关，例如出血和血栓形成、阿尔茨海默病、败血症、多发性硬化症和 COVID-19。APC、凝血酶和 fXa 在凝血和各种疾病中的个体活性很难确定，因为这些蛋白酶是相关的并且具有相似的底物偏好。所以，开发能够成像和区分生物样品中凝血因子的选择性化学工具可以更好地了解它们在各种条件下的作用，并可能有助于建立新的诊断测试。在我们的研究中，我们使用了大量非天然氨基酸，这使我们能够广泛探索酶活性位点的结合口袋。基于获得的特异性谱，我们设计了高选择性底物、抑制剂和基于荧光活性的探针 (ABP)，用于快速、直接和同时检测人血浆中的 APC、凝血酶和 fXa。这使我们能够广泛探索酶活性位点的结
• Furin-targeting activity-based probes with phosphonate and phosphinate esters as warheads
  作者：Shanping Ji、Steven H. L. Verhelst

  DOI：10.1039/d3ob00948c

  日期：——

  Activity-based probes (ABPs) are covalent chemical tools that are widely used to target proteases in chemical biology. Here, we report a series of novel ABPs for the serine protease furin with phosphonate and phosphinate esters as reactive electrophiles. We show that these probes covalently label furin and have nanomolar potencies, because of proposed interactions with the different recognition pockets around

  基于活性的探针 (ABP) 是共价化学工具，广泛用于化学生物学中的靶向蛋白酶。在这里，我们报道了一系列以膦酸酯和次膦酸酯作为反应性亲电子试剂的丝氨酸蛋白酶弗林蛋白酶的新型 ABP。我们表明，这些探针共价标记弗林蛋白酶并具有纳摩尔效力，因为所提出的与弗林蛋白酶活性位点周围不同识别袋的相互作用。
• Small, Potent, and Selective Diaryl Phosphonate Inhibitors for Urokinase-Type Plasminogen Activator with In Vivo Antimetastatic Properties
  作者：Jurgen Joossens、Omar M. Ali、Ibrahim El-Sayed、Georgiana Surpateanu、Pieter Van der Veken、Anne-Marie Lambeir、Buddy Setyono-Han、John A. Foekens、Anneliese Schneider、Wolfgang Schmalix、Achiel Haemers、Koen Augustyns

  DOI：10.1021/jm700962j

  日期：2007.12.27

  A set of small nonpeptidic diaryl phosphonate inhibitors was prepared. Some of these inhibitors show potent and highly selective irreversible uPA inhibition. The biochemical and modeling data prove that the combination of a benzylguanidine moiety with a diaryl phosphonate ester results in optimized molecules for derivatizing the serine alcohol in the uPA active site. Selected compounds show significant antimetastatic effects in the BN-472 rat mammary carcinoma model. We report in this paper a preclinical proof of concept that selective, irreversible uPA inhibitors could be valuable in antimetastatic therapy.
• Development of Irreversible Diphenyl Phosphonate Inhibitors for Urokinase Plasminogen Activator
  作者：J. Joossens、P. Van der Veken、A.-M. Lambeir、K. Augustyns、A. Haemers

  DOI：10.1021/jm0499209

  日期：2004.5.1

  In this letter we report the synthesis and biochemical evaluation of selective, irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator (uPA). A diphenyl phosphonate group was introduced on the substratelike peptide Z-D-Ser-Ala-Arg, and modification of the guanidine side chain was investigated. A guanylated benzyl group appeared the most promising side chain modification. A k(app) value in the 10(3) M-1 s(-1) range for uPA was obtained, together with a selectivity index higher than 240 toward other trypsin-like proteases such as tPA, thrombin, plasmin, and FXa.