(5-Amino-1-benzyloxycarbonylamino-pentyl)-phosphonic acid diphenyl ester | 149194-47-8

• 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: (5-Amino-1-benzyloxycarbonylamino-pentyl)-phosphonic acid diphenyl ester
• 英文别名: benzyl N-(5-amino-1-diphenoxyphosphorylpentyl)carbamate
• CAS: 149194-47-8
• 化学式: C₂₅H₂₉N₂O₅P
• 分子量: 468.489
• InChiKey: RNBVSRFJPOOHSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5-Amino-1-benzyloxycarbonylamino-pentyl)-phosphonic acid diphenyl ester 在 palladium on activated charcoal TEA 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 8.17h， 生成 diphenyl (N-benzyloxycarbonyl-L-alanyl)amino-(4-(N,N'-bis(tert-butyloxycarbonyl)guanyl)butyl)methanephosphonate
  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 肼 作用下， 以 溶剂黄146 为溶剂， 生成 (5-Amino-1-benzyloxycarbonylamino-pentyl)-phosphonic acid diphenyl ester
  参考文献：
  名称：

  Development of activity-based probes for trypsin-family serine proteases

  摘要：

  A series of diphenylphosphonate-based probes were developed for the trypsin-like serine proteases. These probes selectively target serine proteases rather than general serine hydrolases that are targets for fluorophosphonate-based probes. This increased selectivity allows detection of low abundance serine proteases in complex proteomes using simple SIDS-PAGE methods. We present here the application of multiple probes in enzyme activity profiling of intact mast cells, a type of inflammatory cell implicated in allergy and autoimmune diseases. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.012

文献信息

• 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。
• Synthesis and Structure–Activity Relationships of Phosphonic Arginine Mimetics as Inhibitors of the M1 and M17 Aminopeptidases from <i>Plasmodium falciparum</i>
  作者：Komagal Kannan Sivaraman、Alessandro Paiardini、Marcin Sieńczyk、Chiara Ruggeri、Christine A. Oellig、John P. Dalton、Peter J. Scammells、Marcin Drag、Sheena McGowan

  DOI：10.1021/jm4005972

  日期：2013.6.27

  The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the SI pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.
• Synthesis and Evaluation of Diphenyl Phosphonate Esters as Inhibitors of the Trypsin-like Granzymes A and K and Mast Cell Tryptase
  作者：Delwin S. Jackson、Stephanie A. Fraser、Li-Ming Ni、Chih-Min Kam、Ulrike Winkler、David A. Johnson、Christopher J. Froelich、Dorothy Hudig、James C. Powers

  DOI：10.1021/jm970543s

  日期：1998.6.1

  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.
• A convenient synthesis of N-protected diphenyl phosphonate ester analogues of ornithine, lysine and homolysine.
  作者：Robert Hamilton、Brian J. Walker、Brian Walker

  DOI：10.1016/s0040-4039(00)73578-7

  日期：1993.4

  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.
• 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.