benzyl 2-(N-benzyloxycarbonylamino)-4-{[4-(benzyloxycarbonylmethyl)phenyl](methyl)phosphono}butanoate | 926281-38-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl 2-(N-benzyloxycarbonylamino)-4-{[4-(benzyloxycarbonylmethyl)phenyl](methyl)phosphono}butanoate
• 英文别名: benzyl 2-(N-benzyloxycarbonylamino)-4-{[4-(benzyloxycarbonylmethyl)phenyl] (methyl)phosphono}butanoate；benzyl 4-[methoxy-[4-(2-oxo-2-phenylmethoxyethyl)phenoxy]phosphoryl]-2-(phenylmethoxycarbonylamino)butanoate
• CAS: 926281-38-1
• 化学式: C₃₅H₃₆NO₉P
• 分子量: 645.646
• InChiKey: IBRHDEHKMOJVOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  46
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  benzyl 2-(N-benzyloxycarbonylamino)-4-{[4-(benzyloxycarbonylmethyl)phenyl](methyl)phosphono}butanoate 在 5%-palladium/activated carbon 氢气 作用下， 以 溶剂黄146 为溶剂， 反应 3.5h， 以64%的产率得到2-amino-4-{[4-(carboxymethyl)phenyl](methyl)phosphono}butanoic acid
  参考文献：
  名称：

  PHOSPHONIC ACID DIESTER DERIVATIVE AND METHOD FOR PRODUCING THEREOF

  摘要：

  一个由下列一般公式（1）表示的膦酸二酯衍生物，其中R1和R2中至少有一个表示一个离去基团。

  公开号：

  US20090163725A1
• 作为产物：
  描述：

  benzyl 2-benzyloxycarbonylamino-4-(dihydroxyphosphoryl)butanoate 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 benzyl 2-(N-benzyloxycarbonylamino)-4-{[4-(benzyloxycarbonylmethyl)phenyl](methyl)phosphono}butanoate
  参考文献：
  名称：

  Phosphonate-based irreversible inhibitors of human γ-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity

  摘要：

  gamma-Glutamyl transpeptidase (GGT, EC 2.3.2.2) that catalyzes the hydrolysis and transpeptidation of glutathione and its S-conjugates is involved in a number of physiological and pathological processes through glutathione metabolism and is an attractive pharmaceutical target. We report here the evaluation of a phosphonate-based irreversible inhibitor, 2-amino-4-([3-(carboxymethyl)phenoxy](methoyl)phosphoryl}butanoic acid (GGsTop) and its analogues as a mechanism-based inhibitor of human GGT. GGsTop is a stable compound, but inactivated the human enzyme significantly faster than the other phosphonates, and importantly did not inhibit a glutamine amidotransferase. The structure-activity relationships, X-ray crystallography with Escherichia coli GGT, sequence alignment and site-directed mutagenesis of human GGT revealed a critical electrostatic interaction between the terminal carboxylate of GGsTop and the active-site residue Lys562 of human GGT for potent inhibition. GGsTop showed no cytotoxicity toward human fibroblasts and hepatic stellate cells up to 1 mM. GGsTop serves as a non-toxic, selective and highly potent irreversible GGT inhibitor that could be used for various in vivo as well as in vitro biochemical studies. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.08.050

文献信息

• Phosphonic acid diester derivative and method for producing thereof
  申请人：——

  公开号：US08129557B2

  公开（公告）日：2012-03-06

  A phosphonic acid diester derivative represented by the following general formula (1): wherein at least one of R1 and R2 denotes a leaving group.

  一种磷酸二酯衍生物，其通式表示为（1）：其中R1和R2中至少一个表示为离去基团。
• US8129557B2
  申请人：——

  公开号：US8129557B2

  公开（公告）日：2012-03-06
• [EN] METHODS AND COMPOSITIONS FOR THE TREATMENT OF RESPIRATORY DISEASE<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR LE TRAITEMENT DES MALADIES RESPIRATOIRES
  申请人：UNIV BOSTON

  公开号：WO2008137446A1

  公开（公告）日：2008-11-13

  [EN] Disclosed herein are methods and compositions for the treatment of diseases or disorders involving disturbances in glutathione (GSH) metabolism and oxidative stress, especially respiratory diseases or disorders, and most especially asthma. In particular embodiments, methods are disclosed for the treatment of respiratory diseases or disorders, involving the step of administering an agent that inhibits gamma glutamyl transpeptidase (GGT) activity in lung and airway lining fluid.
  [FR] L'invention concerne des procédés et des compositions pour le traitement de maladies ou autres troubles impliquant des perturbations du métabolisme de la glutathione (GSH) et le stress oxydatif, notamment les maladies ou troubles respiratoires, et plus particulièrement, l'asthme. Dans des modes de réalisation particuliers, les procédés proposés impliquent l'étape consistant à administrer un agent qui inhibe l'activité gamma glutamyl transpeptidase (GGT) dans les poumons et le fluide tapissant les voies aériennes.