N-(p-Methoxyphenylsulfonyl)glycine ethyl ester | 161315-27-1

• 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: N-(p-Methoxyphenylsulfonyl)glycine ethyl ester
• 英文别名: ethyl 2-(4-methoxyphenylsulfonamido)acetate；ethyl ((4-methoxyphenyl)sulfonyl)glycinate；ethyl 2-[[4-methoxybenzenesulfonyl]amino]acetate；Ethyl (((4-methoxyphenyl)sulfonyl)amino)acetate；ethyl 2-[(4-methoxyphenyl)sulfonylamino]acetate
• CAS: 161315-27-1
• 化学式: C₁₁H₁₅NO₅S
• mdl: MFCD00978253
• 分子量: 273.31
• InChiKey: VGISMSHTCXXLOR-UHFFFAOYSA-N

物化性质

• 沸点：
  408.4±55.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(p-Methoxyphenylsulfonyl)glycine ethyl ester 在 溴 、 N,N-二异丙基乙胺 作用下， 以 四氯化碳 、 甲苯 为溶剂， 反应 2.5h， 生成 [(E)-4-Methoxy-benzenesulfonylimino]-acetic acid ethyl ester
  参考文献：
  名称：

  Asymmetric α-substitution versus aza Diels–Alder reaction of electron deficient N-sulfonyl imines

  摘要：

  在光解条件下，几种 N-芳磺酰甘氨酸酯被溴化，生成相应的 δ-溴甘氨酸。这些溴化酯可以用一系列碱处理，在原位生成 N-磺酰亚胺酯；试图分离出纯净状态的亚胺的尝试普遍不成功。亚胺一旦生成，就可以与环戊二烯反应，生成相应的氮杂 DielsâAlder 加合物，根据所用碱的不同，产率也不同。此外，如果使用有机金属碱（烷基锂和烷基铝试剂），不仅可以生成氮杂 DielsâAlder 加合物，还可以观察到亚胺的加成反应。在有机铝试剂中，亚胺加成是主要产物。通过在原位生成手性铝试剂，形成三烷基（或三烷氧基）铝试剂，该试剂与 N-磺酰基溴甘氨酸反应后，相应的取代甘氨酸产物的对映体过量率为 19% 至 62%，从而将这一过程转化为化学计量不对称版本。

  DOI：

  10.1039/a909116e
• 作为产物：
  描述：

  4-甲氧基苯乙磺酰氯 、 2-胺基乙酸乙酯 在 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 以88%的产率得到N-(p-Methoxyphenylsulfonyl)glycine ethyl ester
  参考文献：
  名称：

  A Multidisciplinary Approach to Probing Enthalpy–Entropy Compensation and the Interfacial Mobility Model

  摘要：

  In recent years, interfacial mobility has gained popularity as a model with which to rationalize both affinity in ligand binding and the often observed phenomenon of enthalpy-entropy compensation. While protein contraction and reduced mobility, as demonstrated by computational and NMR techniques respectively, have been correlated to entropies of binding for a variety of systems, to our knowledge, Raman difference spectroscopy has never been included in these analyses. Here, nonresonance Raman difference spectroscopy, isothermal titration calorimetry, and X-ray crystallography were utilized to correlate protein contraction, as demonstrated by an increase in protein interior packing and decreased residual protein movement, with trends of enthalpy-entropy compensation. These results are in accord with the interfacial mobility model and lend additional credence to this view of protein activity.

  DOI：

  10.1021/ja1098287

文献信息

• Arylsulfonamido-substituted hydroxamic acids
  申请人：Ciba-Geigy Corporation

  公开号：US05455258A1

  公开（公告）日：1995-10-03

  Particularly the invention relates to the compounds of formula I ##STR1## (a) wherein Ar is carbocyclic or heterocyclic aryl; R is hydrogen, lower alkyl, carbocyclic aryl-lower alkyl, carbocyclic aryl, heterocyclic aryl, biaryl, biaryl-lower alkyl, heterocyclic aryl-lower alkyl, mono- or poly-halo-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl, hydroxy-lower alkyl, acyloxy-lower alkyl, lower alkoxy-lower alkyl, lower alkyl-(thio, sulfinyl or sulfonyl)-lower alkyl, amino, mono- or di-lower alkylamino)-lower alkyl, acylamino-lower alkyl, (N-lower alkyl-piperazino or N-aryl-lower alkylpiperazino)-lower alkyl, or (morpholino, thiomorpholino, piperidino, pyrrolidino, piperidyl or N-lower alkylpiperidyl)-lower alkyl; R.sub.1 is hydrogen, lower alkyl, carbocyclic aryl-lower alkyl, carbocyclic aryl, heterocyclic aryl, biaryl, biaryl-lower alkyl, heterocyclic aryl-lower alkyl, mono- or poly-halo-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl, hydroxy-lower alkyl, acyloxy-lower alkyl, lower alkoxy-lower alkyl, (carbocyclic or heterocyclic aryl)-lower alkoxy-lower alkyl, lower alkyl-(thio, sulfinyl or sulfonyl)-lower alkyl, (amino, mono- or di-lower alkylamino)-lower alkyl, (N-lower alkyl-piperazino or N-aryl-lower alkylpiperazino)-lower alkyl, (morpholino, thiomorpholino, piperidino, pyrrolidino, piperidyl or N-lower alkylpiperidyl)-lower alkyl, acylamino-lower alkyl, piperidyl or N-lower alkylpiperidyl; R.sub.2 is hydrogen or lower alkyl; pharmaceutically acceptable prodrug derivatives; and pharmaceutically acceptable salts thereof.

  该发明涉及以下式I的化合物：(a)其中Ar是碳环或杂环芳基；R是氢、低烷基、碳环芳基-低烷基、碳环芳基、杂环芳基、联苯、联苯-低烷基、杂环芳基-低烷基、单取代或多取代卤代低烷基、C.sub.3-C.sub.7-环烷基、C.sub.3-C.sub.7-环烷基-低烷基、羟基-低烷基、酰氧基-低烷基、低烷氧基-低烷基、低烷基-(硫、亚砜或砜基)-低烷基、氨基、单取代或双取代低烷氨基)-低烷基、酰胺基-低烷基、(N-低烷基哌嗪基或N-芳基-低烷基哌嗪基)-低烷基，或(morpholino、硫代吗啉、哌啶基、吡咯啶基、哌啶基或N-低烷基哌啶基)-低烷基；R.sub.1是氢、低烷基、碳环芳基-低烷基、碳环芳基、杂环芳基、联苯、联苯-低烷基、杂环芳基-低烷基、单取代或多取代卤代低烷基、C.sub.3-C.sub.7-环烷基、C.sub.3-C.sub.7-环烷基-低烷基、羟基-低烷基、酰氧基-低烷基、低烷氧基-低烷基、(碳环或杂环芳基)-低烷氧基-低烷基、低烷基-(硫、亚砜或砜基)-低烷基、(氨基、单取代或双取代低烷氨基)-低烷基、(N-低烷基哌嗪基或N-芳基-低烷基哌嗪基)-低烷基、(morpholino、硫代吗啉、哌啶基、吡咯啶基、哌啶基或N-低烷基哌啶基)-低烷基、酰胺基-低烷基、哌啶基或N-低烷基哌啶基；R.sub.2是氢或低烷基；药学上可接受的前药衍生物；及其药学上可接受的盐。
• Regioselectivity and the Nature of the Reaction Mechanism in Nucleophilic Substitution Reactions of 2,4-Dinitrophenyl X-Substituted Benzenesulfonates with Primary Amines
  作者：Ik-Hwan Um、Jin-Young Hong、Jung-Joo Kim、Ok-Mi Chae、Sun-Kun Bae

  DOI：10.1021/jo034190i

  日期：2003.6.1

  mechanism. The second-order rate constants for the S-O bond fission result in good linear Yukawa-Tsuno plots for the aminolyses of 2,4-dinitrophenyl X-substituted benzenesulfonates. However, the second-order rate constants for the C-O bond fission show no correlation with the electronic nature of the sulfonyl substituent X, indicating that the C-O bond fission proceeds through an S(N)Ar mechanism in which the

  已经测量了2，4-二硝基苯基X-取代的苯磺酸盐与一系列伯胺的反应的二级速率常数。亲核取代反应通过竞争性SO和CO键裂变途径进行。SO键裂变主要发生在与高碱性胺或与在磺酰基部分中具有强吸电子基团的底物的反应中。另一方面，对于与低碱性胺或与磺酰基部分中具有强供电子基团的底物的反应，CO键裂变会相当多地发生，这强调区域选择性受胺的碱性和氢的电子效应的支配。磺酰基取代基X。SO键裂变的表观二阶速率常数已导致2,4-二硝基苯基苯磺酸盐与10种不同伯胺反应的非线性布朗斯台德图，这表明速率改变步骤在改变时发生变化胺的碱度。与SO键裂变路径相关的微观速率常数（k（1）和k（2）/ k（-）（1）比率）支持所提出的机制。SO键裂变的二级速率常数导致2,4-二硝基苯基X-取代的苯磺酸酯的氨解酶具有良好的线性Yukawa-Tsuno图。但是，CO键裂变的二级速率常数与磺酰基取代基X的电子性质无关，
• Effect of Substituent on Regioselectivity and Reaction Mechanism in Aminolysis of 2,4-Dinitrophenyl X-Substituted Benzenesulfonates
  作者：Ik-Hwan Um、Jin-Young Hong、Jin-Ah Seok

  DOI：10.1021/jo048227q

  日期：2005.2.1

  a kinetic study for the nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzensulfonates (X = 4-MeO, 1a, and X = 4-NO2, 1c) with a series of primary amines in 80 mol % H2O/20 mol % DMSO at 25.0 °C. The reactions proceed through S−O and C−O bond fission pathways competitively. The fraction of the S−O bond fission increases as the attaching amine becomes more basic and the substituent

  我们对的2,4-二硝基苯基X取代的benzensulfonates亲核取代反应的动力学研究报告（X = 4-的MeO，1A，和X = 4-NO 2，1C），在80摩尔％一系列伯胺的在25.0°C下，H 2 O / 20 mol％DMSO。反应通过S-O和C-O键裂变途径竞争地进行。S-O键裂变的分数随连接胺变得更碱性和取代基X从4-MeO变为4-NO 2而增加，表明区域选择性是由取代基X的电子性质以及胺的碱度决定的。已建议S-O键裂变通过加成中间体进行，其中速率确定步骤（RDS）的变化为p K a °= 8.9±0.1。取代基X的电子性质影响k N S - O和k 1值，但不影响k 2 / k - 1比和p K a°值明显。通过供电子取代基和亲电子中心之间的共振相互作用，稳定基态（GS）的原因是1a的反应性比1c降低。C-O键裂变的二阶速率常数与取代基X的电子性质不相关。距离效应和反应机理的性质被认为是造成这种不相关的原因。
• Arylsufonamido-substituted hydroxamic acids
  申请人：Ciba-Geigy Corporation

  公开号：US05506242A1

  公开（公告）日：1996-04-09

  The invention relates to a method of inhibiting metalloellastase activity, of inhibiting the degradation of elastin, or of treating macrophage metalloelastase dependent conditions in mammals which comprises administering to a mammal in need thereof an effective macrophage metalloelastase inhibiting amount of a compound of formula I ##STR1## wherein Ar, R, R.sub.1 and R.sub.2 have meanings as defined, or of a pharmaceutically acceptable prodrug derivative thereof, or of a pharmaceutically acceptable salt thereof, or of pharmaceutical compositions comprising a said compound.

  该发明涉及一种抑制金属弹性蛋白酶活性、抑制弹性蛋白降解或治疗依赖于巨噬细胞金属弹性蛋白酶的哺乳动物病症的方法，包括向需要的哺乳动物施用化合物I的有效巨噬细胞金属弹性蛋白酶抑制剂量，其中Ar、R、R.sub.1和R.sub.2的含义如所定义，或其药学上可接受的前药衍生物，或其药学上可接受的盐，或包括所述化合物的药物组合物。
• Arylsulfonamido-substituted hydroxamix acids
  申请人：Ciba-Geigy Corporation

  公开号：US05646167A1

  公开（公告）日：1997-07-08

  Disclosed are compounds of formula I ##STR1## wherein R, R.sub.1, R.sub.2 and Ar have meanings as defined; pharmaceutically acceptable prodrug derivatives and pharmaceutically acceptable salts thereof; methods for preparation thereof; pharmaceutical compositions comprising said compounds; and methods of inhibiting matrix-degrading metalloproteinase and of treating matrix-degrading metalloproteinase dependent conditions in mammals using such compounds.

  公开的是式I的化合物##STR1##其中R、R.sub.1、R.sub.2和Ar的含义如所定义；其药学上可接受的前药衍生物和药学上可接受的盐；其制备方法；包含所述化合物的药物组合物；以及使用这些化合物抑制基质降解金属蛋白酶和治疗依赖于基质降解金属蛋白酶的哺乳动物病症的方法。