diphenyl benzyloxycarbonylamino-(4-phthalimidobutyl)methanephosphonate | 149194-44-5

• 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-(4-phthalimidobutyl)methanephosphonate
• 英文别名: benzyl N-[5-(1,3-dioxoisoindolin-2-yl)-1-diphenoxyphosphoryl-pentyl]carbamate；benzyl N-[5-(1,3-dioxoisoindol-2-yl)-1-diphenoxyphosphorylpentyl]carbamate
• CAS: 149194-44-5
• 化学式: C₃₃H₃₁N₂O₇P
• 分子量: 598.592
• InChiKey: CNJOZTYNWQXMFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 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-(4-phthalimidobutyl)methanephosphonate 在 氢溴酸 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 0.5h， 生成 N-[5-(1,3-dioxoisoindol-2-yl)-1-[oxido(diphenoxy)phosphaniumyl]pentyl]formamide
  参考文献：
  名称：

  Synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters

  摘要：

  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.

  DOI：

  10.1016/j.tetlet.2006.04.058
• 作为产物：
  描述：

  5-氨基-1-戊醇 在 草酰氯 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 5.0h， 生成 diphenyl benzyloxycarbonylamino-(4-phthalimidobutyl)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

文献信息

• Fluorescent diphenylphosphonate-based probes for detection of serine protease activity during inflammation
  作者：Laura E. Edgington-Mitchell、Nicholas Barlow、Luigi Aurelio、Aminath Samha、Monika Szabo、Bim Graham、Nigel Bunnett

  DOI：10.1016/j.bmcl.2016.11.064

  日期：2017.1

  vitro, they are less valuable for in vivo studies. We used these probes to evaluate serine protease activity in two mouse models of acute inflammation, including pancreatitis and colitis. As anticipated, the activity of trypsin-like proteases was increased during pancreatitis. Levels of elastase-like proteases were low in pancreatic lysates and colonic luminal fluids, whether healthy or inflamed. Exogenously

  基于活性的探针是以活性依赖性方式共价结合蛋白酶活性位点的小分子。我们合成并表征了两种基于荧光活性的探针，它们靶向具有胰蛋白酶样或弹性蛋白酶样活性的丝氨酸蛋白酶。我们评估了这些探针对重组酶的选择性和效力，并证明虽然它们在体外有效标记复杂蛋白质混合物中的活性蛋白酶，但它们在体内的价值较低。学习。我们使用这些探针来评估两种急性炎症小鼠模型（包括胰腺炎和结肠炎）中的丝氨酸蛋白酶活性。正如预期的那样，胰蛋白酶样蛋白酶的活性在胰腺炎期间增加。无论是健康的还是发炎的，胰腺裂解物和结肠腔液中的弹性蛋白酶样蛋白酶水平都很低。外源添加的重组中性粒细胞弹性蛋白酶在与这些样品孵育后受到抑制，与对照相比，这种效果在发炎样品中得到增强。这些数据表明内源性抑制剂和弹性蛋白酶降解蛋白酶在炎症过程中被上调。
• MOLECULARLY IMPRINTED POLYMERS, METHODS FOR THEIR PRODUCTION AND USES THEREOF
  申请人：Hearn Milton T.W.

  公开号：US20120225962A1

  公开（公告）日：2012-09-06

  The present invention relates to methods of preparing molecularly imprinted polymers (MIPs) which facilitate chemical hydrolysis and more particularly the hydrolysis of chemical substrates which possess hydrolytically labile bonds such as peptides and proteins. The present invention is thus directed to MIPs designed to possess hydrolytic activity, methods for preparing such MIPs and uses of the MIPs.

  本发明涉及制备分子印迹聚合物（MIPs）的方法，该方法促进化学水解，更具体地，促进具有水解敏感键的化学底物（例如肽和蛋白质）的水解。因此，本发明针对设计具有水解活性的MIPs，制备这种MIPs的方法以及MIPs的用途。
• 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.