diphenyl {[(benzyloxy)carbonyl]amino}[4-(tert-butoxycarbonyl)aminophenyl]methylphosphonate | 695171-94-9

• 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: diphenyl {[(benzyloxy)carbonyl]amino}[4-(tert-butoxycarbonyl)aminophenyl]methylphosphonate
• 英文别名: diphenyl benzyloxycarbonylamino-(4-(tert-butyloxycarbonylamino)phenyl)methanephosphonate；benzyl((4-(tert-butoxycarbonyl)aminophenyl)(diphenoxyphosphoryl)methyl)carbamate；benzyl N-[diphenoxyphosphoryl-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]methyl]carbamate
• CAS: 695171-94-9
• 化学式: C₃₂H₃₃N₂O₇P
• 分子量: 588.597
• InChiKey: POGLEOFDGLXEAN-UHFFFAOYSA-N

物化性质

• 沸点：
  693.5±55.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)

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：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diphenyl {[(benzyloxy)carbonyl]amino}[4-(tert-butoxycarbonyl)aminophenyl]methylphosphonate 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 、 乙腈 为溶剂， 反应 11.17h， 生成 diphenyl (N-benzyloxycarbonyl-L-alanyl)amino-(4-(N,N'-bis(tert-butyloxycarbonyl)guanyl)phenyl)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：

  对氨基苯甲醇 在 copper(II) bis(trifluoromethanesulfonate) 、 戴斯-马丁氧化剂 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 diphenyl {[(benzyloxy)carbonyl]amino}[4-(tert-butoxycarbonyl)aminophenyl]methylphosphonate
  参考文献：
  名称：

  [EN] NOVEL KLK4 INHIBITORS
  [FR] NOUVEAUX INHIBITEURS DE KLK4

  摘要：

  本发明涉及具有共同化学结构的新化合物和探针，这种结构对于获得强大的对KLK4的抑制活性是必要的，或者可用于检测KLK4肽及其活性。它进一步涉及利用这些化合物和方法通过利用所述的探针或抑制剂来抑制和/或检测体外和体内的KLK4活性。本发明的化合物与先前的化合物不同，至少在于存在苯基胍（而不是苄基胍等）和/或尾基中存在杂原子，它们的共同存在意外地导致强大和选择性的KLK4抑制活性。

  公开号：

  WO2015144933A1

文献信息

• Lewis Acid Catalyzed Synthesis of N-Protected Diphenyl 1-Aminoalkyl­phosphonates
  作者：Achiel Haemers、Pieter Van der Veken、Ibrahim El Sayed、Jurgen Joossens、Christian Stevens、Koen Augustyns

  DOI：10.1055/s-2004-837307

  日期：——

  Diphenyl α-aminomethylphosphonates are prepared in good yields using a Lewis acid catalyzed Birum-Oleksyszyn reaction. This approach enlarges the scope of this reaction, allowing the use of aldehydes and ketones and the use of acid-labile groups in the synthesis of mono-and disubstituted diphenyl 1-aminoalkylphosphonates.

  二苯基α-氨甲基膦酸酯通过路易斯酸催化的Birum-Oleksyszyn反应以良好的收率制备。这种方法扩大了该反应的适用范围，允许使用醛和酮，并在合成单取代和双取代的二苯基1-氨基烷基膦酸酯时使用耐酸性基团。
• 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.
• [EN] NOVEL KLK4 INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE KLK4
  申请人：UNIV ANTWERPEN

  公开号：WO2015144933A1

  公开（公告）日：2015-10-01

  The present invention relates to novel compounds and probes which have a common chemical structure necessary to obtain potent inhibitory activity against KLK4 and/or may be used for the detection of KLK4 peptides and their activity. It further relates to the use of these compounds and methods for inhibiting and/or detecting KLK4 activity in vitro and in vivo by making use of said probes or inhibitors. The compounds of the invention differ from prior art compounds at least in the presence of phenyl guanidine (instead of e.g. benzyl guanidine) and/or the presence of a heteroatom in the tail group, their combined presence unexpectedly leading to potent and selective KLK4 inhibitory activity.

  本发明涉及具有共同化学结构的新化合物和探针，这种结构对于获得强大的对KLK4的抑制活性是必要的，或者可用于检测KLK4肽及其活性。它进一步涉及利用这些化合物和方法通过利用所述的探针或抑制剂来抑制和/或检测体外和体内的KLK4活性。本发明的化合物与先前的化合物不同，至少在于存在苯基胍（而不是苄基胍等）和/或尾基中存在杂原子，它们的共同存在意外地导致强大和选择性的KLK4抑制活性。