triethyl phosphonothiolformate | 163678-85-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: triethyl phosphonothiolformate
• 英文别名: S-ethyl diethoxyphosphorylmethanethioate
• CAS: 163678-85-1
• 化学式: C₇H₁₅O₄PS
• 分子量: 226.233
• InChiKey: DXFKTYZWOJEWAW-UHFFFAOYSA-N

物化性质

• 沸点：
  278.6±23.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  77.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  triethyl phosphonothiolformate 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以92%的产率得到S-ethyl diethoxythiophosphorylthioformate
  参考文献：
  名称：

  Alberti, Angelo; Benaglia, Massimo; Hapiot, Philippe, Journal of the Chemical Society. Perkin Transactions 2 (2001), 2000, # 9, p. 1908 - 1913

  摘要：

  DOI：
• 作为产物：
  描述：

  亚磷酸三乙酯 以68%的产率得到
  参考文献：
  名称：

  Kowalenko L. W., Buwashkina N. I., Sosnow A. W., Zh. obshh. khimii, 64 (1994) N 10, S 1634-1638

  摘要：

  DOI：

文献信息

• Compositions comprising oxophosphonate-based metalloproteinase inhibitors
  申请人：Yissum Research Development Company of the Hebrew University of Jerusalem

  公开号：US07101864B1

  公开（公告）日：2006-09-05

  The present invention relates to compositions useful for treating or controlling disease states or conditions associated with zinc containing proteinases, especially metalloproteinases. The active ingredient in these compositions is an alpha-oxo- or alpha-thixophosphpnate of formula (I). Out of the phosphonates of formula (I), some are known and others are new. The novel compounds constitute another aspect of the invention.

  本发明涉及用于治疗或控制与含锌蛋白酶，特别是金属蛋白酶相关的疾病状态或病况的组合物。这些组合物中的活性成分是具有化学式(I)的α-氧代或α-硫代膦酸酯。在化学式(I)的膦酸酯中，有些是已知的，而另一些是新的。这些新化合物构成了本发明的另一个方面。
• Carbamoylphosphonates, a New Class of in Vivo Active Matrix Metalloproteinase Inhibitors. 1. Alkyl- and Cycloalkylcarbamoylphosphonic Acids
  作者：Eli Breuer、Claudio J. Salomon、Yiffat Katz、Weibin Chen、Shuiming Lu、Gerd-Volker Röschenthaler、Rivka Hadar、Reuven Reich

  DOI：10.1021/jm030386z

  日期：2004.5.1

  Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent enzymes that hydrolyze connective tissue and are involved in a variety of diseases, which are associated with undesired tissue breakdown. This paper reports the synthesis, characterization, and biological evaluation of a novel class of MMP inhibitors based on the carbamoylphosphonic acid function. We report a series of 10 open

  基质金属蛋白酶（MMP）是一类20多种依赖锌的酶，它们水解结缔组织，并参与多种疾病，这些疾病与不良的组织分解有关。本文报告了基于氨基甲酰基膦酸功能的一类新型MMP抑制剂的合成，表征和生物学评估。我们报告一系列10开链N-烷基氨基甲酰基膦酸（范围从R = C（1）到C（6）基团），八个N-环烷基氨基甲酰基膦酸（范围从环丙基到环辛基环）和四个N，N-二烷基氨基甲酰基膦酸酸。在三种体外模型中评估了这些化合物，这些模型包括：（a）跨重构基膜的体外侵袭，（b）测定重组MMP-1，MMP-2，MMP-3的IC（50）值， MMP-8和MMP-9酶，（c）体外毛细血管形成模型，其是血管生成的模型。还在体内鼠黑色素瘤模型中测试了几种化合物。得出以下一般结论：大多数化合物对MMP-2的选择性优于其他MMP亚型。环烷基氨基甲酰基膦酸比类似的开链烷基化合物更有效。N-环戊基氨基甲酰基膦酸（3m）显示出在环烷基衍
• Aminoalkylcarbamoylphosphonates reduce TNFα release from activated immune cells
  作者：Efrat Harel、Abraham Rubinstein、Weibin Chen、Eli Breuer、Boaz Tirosh

  DOI：10.1016/j.bmcl.2010.09.048

  日期：2010.11

  Some carbamoylphosphonates (CPOs) inhibit matrix metalloproteinases (MMPs). Although MMPs are involved in inflammatory processes, the anti-inflammatory activity of CPOs has not been reported. In this context we compared the biological activity of the three aminoCPOs, PYR-CPO, PIP-CPO and cis-ACCP. We were particularly interested in their capability to modulate the secretion of tumor necrosis factor alpha (TNF alpha). LPS-activated mouse peritoneal macrophages and LPS-activated mouse splenocytes were used to explore this question. It was found that the aminoCPOs were able to reduce TNF alpha secretion to a level equivalent to the reduction caused by the steroid drug budesonide (BUD). The reduction in TNF alpha levels was neither accompanied by cytotoxicity, nor did it inhibit cell proliferation. To explicate whether the aminoCPOs affect TNF alpha processing by TNF alpha-converting enzyme (TACE), TACE inhibitory properties of the three molecules was tested in vitro. Only PIP-CPO exerted TACE inhibitory activity at therapeutic (non-cytotoxic) concentrations, indicating on its potential to serve as an anti-inflammatory agent by reducing TNF alpha secretion. (C) 2010 Elsevier Ltd. All rights reserved.
• Carbamoylphosphonate MMP inhibitors. Part 4: The influence of chirality and geometrical isomerism on the potency and selectivity of inhibition
  作者：Eli Breuer、Yiffat Katz、Rivka Hadar、Reuven Reich

  DOI：10.1016/j.tetasy.2004.07.002

  日期：2004.8

  Matrix metalloproteinases (MMPs) are a family of over twenty zinc-dependent enzymes that hydrolyze connective tissue and are involved in a variety of diseases, which are associated with undesired tissue breakdown. Previously we described the synthesis of a series of achiral alkyl and cycloalkylcarbamoylphosphonic acids and their biological evaluation. Herein we report the effect of chirality and geometrical isomerism on the potency and selectivity of inhibition. The inhibitory potencies of pairs of enantiomeric and stereoisomeric alkyl and cycloalkylcarbamoylphosphonic acids were evaluated on recombinant MMP-1, MMP-2, MMP-3. MMP-8, and MMP-9 enzymes. The results show that the enantiomers and stereoisomers studied differ considerably in their inhibitory potencies and selectivities on the enzyme subtypes studied. Such a result is consistent with the assumption that the carbamoylphosphonates interact with a chiral environment such as an enzyme. (C) 2004 Elsevier Ltd. All rights reserved.
• Design and synthesis of non-hydroxamate histone deacetylase inhibitors: identification of a selective histone acetylating agent
  作者：Takayoshi Suzuki、Azusa Matsuura、Akiyasu Kouketsu、Shinya Hisakawa、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1016/j.bmc.2005.04.002

  日期：2005.7

  A series of suberoylanilide hydroxamic acid (SAHA)-based non-hydroxamates was designed, synthesized, and evaluated for their histone deacetylase (HDAC) inhibitory activity. Among these, methyl sulfoxide 15 inhibited HDACs in enzyme assays and caused hyperacetylation of histone H4 while not inducing the accumulation of acetylated alpha-tubulin in HCT116 cells. (c) 2005 Elsevier Ltd. All rights reserved.