diphenyl benzyloxycarbonylamino-(3-phthalimidopropyl)methanephosphonate | 149194-43-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: diphenyl benzyloxycarbonylamino-(3-phthalimidopropyl)methanephosphonate
• 英文别名: benzyl N-[4-(1,3-dioxoisoindol-2-yl)-1-diphenoxyphosphorylbutyl]carbamate
• CAS: 149194-43-4
• 化学式: C₃₂H₂₉N₂O₇P
• 分子量: 584.565
• InChiKey: INASFYBBUKWTFD-UHFFFAOYSA-N

物化性质

• 沸点：
  748.2±60.0 °C(predicted)
• 密度：
  1.327±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diphenyl benzyloxycarbonylamino-(3-phthalimidopropyl)methanephosphonate 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 生成 2-[4-Amino-4-[oxido(diphenoxy)phosphaniumyl]butyl]isoindole-1,3-dione
  参考文献：
  名称：

  A convenient synthesis of N-protected diphenyl phosphonate ester analogues of ornithine, lysine and homolysine.

  摘要：

  A 3-step synthesis to the title compounds has been developed which provides them differentially protected at nitrogen. These could then be selectively deprotected using hydrazine hydrate or hydrogenolysis over Pd/C.

  DOI：

  10.1016/s0040-4039(00)73578-7
• 作为产物：
  描述：

  2-(4-羟基丁基)-1H-异吲哚-1,3(2H)-二酮 在 草酰氯 、 溶剂黄146 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 反应 1.75h， 生成 diphenyl benzyloxycarbonylamino-(3-phthalimidopropyl)methanephosphonate
  参考文献：
  名称：

  Synthesis and Evaluation of Diphenyl Phosphonate Esters as Inhibitors of the Trypsin-like Granzymes A and K and Mast Cell Tryptase

  摘要：

  Thirty-six new amino acid and peptidyl diphenyl phosphonate esters were synthesized and evaluated to identify potent and selective inhibitors for four trypsin-like proteases: lymphocyte granzymes A and K, human mast cell tryptase, and pancreatic trypsin. Among five Cbz derivatives of Lys and Arg homologues, Z-(4-AmPhe)(P)(OPh)(2) is the mast potent inhibitor for granzyme A, and Z-Lys(P)(OPh)(2) is the best inhibitor for granzyme K, mast tryptase, and trypsin. The amidino P1 residue D,L-(4-AmPhGly)(P)(OPh)(2) was utilized in a series of compounds with several different N-protecting groups and systematic substitutions at P2 in Cbz-AA derivatives and at P3 in Cbz-AA-Ala derivatives. Generally, these phosphonates inhibit granzyme A and trypsin more potently than granzyme K and tryptase. The P2 Thr and Ala dipeptide phosphonates, Cbz-AA-(4-AmPhGly)(P)(OPh)(2), are the most potent inhibitors for granzyme A, and Cbz-Thr-(4-AmPhGly)(P)(OPh)(2) (k(obs)/[I] = 2220 M-1 s(-1)) was quite specific with much lower inhibition rates for granzyme K and trypsin (k(obs)/[I] = 3 and 97 M-1 s(-1), respectively) and no inhibition with tryptase. The most effective inhibitor of granzyme A was Ph-SO2-Gly-Pro-(4-AmPhGly)(P)(OPh)(2) with a second-order rate constant of 3650 M-1 s(-1). The most potent inhibitor for granzyme K was 3,3-diphenylpropanoyl-Pro-(4-AmPhGly)(P)(OPh)(2) with a k(obs)/[I] = 1830 M-1 s(-1) all other phosphonates inhibited granzyme K weakly (k(obs)[I] < 60 M-1 s(-1)). Human mast cell tryptase was inhibited slowly by these phosphonates with Cbz-Lys(P)(OPh)(2) as the best inhibitor (k(obs)/[I] = 89 M-1 s(-1)). The overall results suggest that scaffolds of Phe-Thr-(4-AmPhe) and Phe-Pro-Lys will be useful to create selective phosphonate inhibitors for granzymes A and K, respectively, and that P4 substituents offer opportunities to further enhance selectivity and reactivity.

  DOI：

  10.1021/jm970543s

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。
• 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.
• Synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters
  作者：Marcin Sieńczyk、Maciej Kliszczak、Józef Oleksyszyn

  DOI：10.1016/j.tetlet.2006.04.058

  日期：2006.6

  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.
• A KLK6 Activity-Based Probe Reveals a Role for KLK6 Activity in Pancreatic Cancer Cell Invasion
  作者：Leran Zhang、Scott Lovell、Elena De Vita、Pravin Kumar Ankush Jagtap、Daniel Lucy、Andrea Goya Grocin、Svend Kjær、Annabel Borg、Janosch Hennig、Aubry K. Miller、Edward W. Tate

  DOI：10.1021/jacs.2c07378

  日期：2022.12.14
• COMPOUNDS FOR DETECTING PROTEASES
  申请人：The Queen's University Of Belfast

  公开号：EP2470672B1

  公开（公告）日：2016-10-12