tert-butyl N-[N'-[4-[amino-[oxido(diphenoxy)phosphaniumyl]methyl]phenyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate

• 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 N-[N'-[4-[amino-[oxido(diphenoxy)phosphaniumyl]methyl]phenyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• 化学式: C₃₀H₃₇N₄O₇P
• 分子量: 596.62
• InChiKey: SFUCAQSKJPFQHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[N'-[4-[amino-[oxido(diphenoxy)phosphaniumyl]methyl]phenyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate 在 palladium on activated charcoal TEA 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.34h， 生成 diphenyl ((N-benzyloxycarbonyl-D-seryl)-L-alanyl)amino-(4-guanylphenyl)methanephosphonate trifluoroacetate
  参考文献：
  名称：

  Development of Irreversible Diphenyl Phosphonate Inhibitors for Urokinase Plasminogen Activator

  摘要：

  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.

  DOI：

  10.1021/jm0499209
• 作为产物：
  描述：

  亚磷酸三苯酯 在 palladium on activated charcoal 、 水 、 溶剂黄146 、 三乙胺 、 mercury dichloride 、 tin(ll) chloride 作用下， 以 乙酸乙酯 为溶剂， 生成 tert-butyl N-[N'-[4-[amino-[oxido(diphenoxy)phosphaniumyl]methyl]phenyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
  参考文献：
  名称：

  以膦酸酯和次膦酸酯为弹头的弗林蛋白酶靶向活性探针

  摘要：

  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。

  DOI：

  10.1039/d3ob00948c

文献信息

• Phosphonate inhibitors of West Nile virus NS2B/NS3 protease
  作者：Marcin Skoreński、Aleksandra Milewska、Krzysztof Pyrć、Marcin Sieńczyk、Józef Oleksyszyn

  DOI：10.1080/14756366.2018.1506772

  日期：2019.1.1

  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.
• A convenient synthesis of new α-aminoalkylphosphonates, aromatic analogues of arginine as inhibitors of trypsin-like enzymes
  作者：Marcin Sienczyk、Jozef Oleksyszyn

  DOI：10.1016/j.tetlet.2004.08.021

  日期：2004.9

  A simple and efficient protocol for the synthesis of new N-protected alpha-aminoalkylphosphonic diphenyl esters-aromatic analogues of arginine-is presented. The crucial, guanylating step was achieved using S-ethyl-N,N'-di(Boc)isothiourea in chloroform and in the presence of Et3N and HgCl2. Deprotection of the derivatives obtained was performed using trifluoroacetic acid in CH2Cl2 or hydrogenolysis over Pd/C. The products are potent inhibitors of trypsin. (C) 2004 Elsevier Ltd. All rights reserved.
• 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.
• 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。