benzyl (2RS,R_PS_P)-2-benzyloxycarbonylamino-4-{[3-(benzyloxycarbonyl)phenoxy](methoxy)phosphoryl}butanoate | 940963-70-2

• 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 (2RS,R_PS_P)-2-benzyloxycarbonylamino-4-{[3-(benzyloxycarbonyl)phenoxy](methoxy)phosphoryl}butanoate
• 英文别名: benzyl 2-(N-benzyloxycarbonylamino)-4-{[3-(benzyloxycarbonyl)phenyl](methyl)phosphono} butanoate；Benzyl 3-[methoxy-[4-oxo-4-phenylmethoxy-3-(phenylmethoxycarbonylamino)butyl]phosphoryl]oxybenzoate；benzyl 3-[methoxy-[4-oxo-4-phenylmethoxy-3-(phenylmethoxycarbonylamino)butyl]phosphoryl]oxybenzoate
• CAS: 940963-70-2
• 化学式: C₃₄H₃₄NO₉P
• 分子量: 631.619
• InChiKey: NPBYFYQEUYDNHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  45
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 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 (2RS,R_PS_P)-2-benzyloxycarbonylamino-4-{[3-(benzyloxycarbonyl)phenoxy](methoxy)phosphoryl}butanoate 在 5%-palladium/activated carbon 氢气 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 3.0h， 以90%的产率得到(2RS,R_PS_P)-2-amino-4-[(3-carboxyphenoxy)(methoxy)phosphoryl]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-(N-benzyloxycarbonylamino)-4-[chloro(methyl)phosphono]butanoate 、 3-羟基苯甲酸苄酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.75h， 以40%的产率得到benzyl (2RS,R_PS_P)-2-benzyloxycarbonylamino-4-{[3-(benzyloxycarbonyl)phenoxy](methoxy)phosphoryl}butanoate
  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

文献信息

• 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
  作者：Akane Kamiyama、Mado Nakajima、Liyou Han、Kei Wada、Masaharu Mizutani、Yukiko Tabuchi、Akiko Kojima-Yuasa、Isao Matsui-Yuasa、Hideyuki Suzuki、Keiichi Fukuyama、Bunta Watanabe、Jun Hiratake

  DOI：10.1016/j.bmc.2016.08.050

  日期：2016.11

  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.
• PHOSPHONIC ACID DIESTER DERIVATIVE AND METHOD FOR PRODUCING THEREOF
  申请人：Hiratake Jun

  公开号：US20090163725A1

  公开（公告）日：2009-06-25

  A phosphonic acid diester derivative represented by the following general formula (1): wherein at least one of R 1 and R 2 denotes a leaving group.

  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。