N-(4-phenoxybenzenesulfonyl)iminodiacetic acid | 914380-10-2

• 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: N-(4-phenoxybenzenesulfonyl)iminodiacetic acid
• 英文别名: {[4-Phenoxy-benzenesulphonyl]-carboxymethyl-amino}-acetic acid；2-[carboxymethyl-(4-phenoxyphenyl)sulfonylamino]acetic acid
• CAS: 914380-10-2
• 化学式: C₁₆H₁₅NO₇S
• 分子量: 365.364
• InChiKey: OSXBLPMIZWEOSW-UHFFFAOYSA-N

物化性质

• 熔点：
  148-151 °C
• 沸点：
  609.9±65.0 °C(Predicted)
• 密度：
  1.474±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(4-phenoxybenzenesulfonyl)iminodiacetic acid 在 N-甲基吗啉 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 N-((benzyloxycarbamoyl)methyl)-N-(4-phenoxybenzenesulfonyl)aminoacetic acid
  参考文献：
  名称：

  Design, synthesis and molecular modeling study of iminodiacetyl monohydroxamic acid derivatives as MMP inhibitors

  摘要：

  As the matrix metalloproteinases (MMPs) can be massively up-regulated in degenerative tissues and degrade the extracellular matrix, these key enzymes are promising targets for the therapy of cancer and other degenerative diseases. Here, we are presenting a series of new non-peptidic hydroxamate-based matrix metalloproteinase inhibitors, MMPIs, incorporating the iminodiacetic (IDA) hydroxamic acid scaffold, as mimics of truncated peptidic MMPIs. A series of alkylaryl and sulfonylaryl groups, on the IDA basic scaffold, was investigated with the aim of improving potency and selectivity against MMPs involved in degenerative diseases. The sulfonamide based IDA derivatives studied (compounds B1-B3) showed to be potent (nM range) against deep S1' pocket MMPs enzymes (i.e., MMP-2). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.07.011
• 作为产物：
  描述：

  二苯醚 在 氯磺酸 、 氢氧化钾 、 氯化亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 N-(4-phenoxybenzenesulfonyl)iminodiacetic acid
  参考文献：
  名称：

  Design, synthesis and molecular modeling study of iminodiacetyl monohydroxamic acid derivatives as MMP inhibitors

  摘要：

  As the matrix metalloproteinases (MMPs) can be massively up-regulated in degenerative tissues and degrade the extracellular matrix, these key enzymes are promising targets for the therapy of cancer and other degenerative diseases. Here, we are presenting a series of new non-peptidic hydroxamate-based matrix metalloproteinase inhibitors, MMPIs, incorporating the iminodiacetic (IDA) hydroxamic acid scaffold, as mimics of truncated peptidic MMPIs. A series of alkylaryl and sulfonylaryl groups, on the IDA basic scaffold, was investigated with the aim of improving potency and selectivity against MMPs involved in degenerative diseases. The sulfonamide based IDA derivatives studied (compounds B1-B3) showed to be potent (nM range) against deep S1' pocket MMPs enzymes (i.e., MMP-2). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.07.011

文献信息

• Carbonic anhydrase inhibitors: Inhibition of cytosolic/tumor-associated isoforms I, II, and IX with iminodiacetic carboxylates/hydroxamates also incorporating benzenesulfonamide moieties
  作者：M. Amelia Santos、Sergio Marques、Daniela Vullo、Alessio Innocenti、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2006.12.107

  日期：2007.3

  sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs), also possessing carboxylate/hydroxamate moieties in their molecule, is reported. These compounds may act on dual antitumor targets, the tumor-associated CA isozymes (CA IX) and some matrix metalloproteinases (MMPs). The compounds were prepared by an original method starting from iminodiacetic acid, and assayed as inhibitors of three isozymes

  据报道，新型磺酰胺碳酸酐酶（CA，EC 4.2.1.1）抑制剂（CAI）的合成，其分子中还具有羧酸盐/异羟肟酸酯部分。这些化合物可能作用于双重抗肿瘤靶标，肿瘤相关的CA同工酶（CA IX）和某些基质金属蛋白酶（MMP）。这些化合物是从亚氨基二乙酸开始采用原始方法制备的，并作为三种同功酶hCA I，II（胞质）和IX（跨膜）的抑制剂进行了分析。新衍生物显示出对同工酶I（K（I）s在95-8300 nM范围内）的弱抑制活性，对中型CA II抑制剂（K（I）s在8.4-65 nM范围内）极好，并且非常好的选择性CA IX抑制剂（K（I）范围为3.8-26 nM）。
• Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques
  作者：Nazanin Hakimzadeh、Victorine A. Pinas、Ger Molenaar、Vivian de Waard、Esther Lutgens、Berthe L. F. van Eck-Smit、Kora de Bruin、Jan J. Piek、Jos L. H. Eersels、Jan Booij、Hein J. Verberne、Albert D. Windhorst

  DOI：10.1371/journal.pone.0187767

  日期：——

  Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice.

  分子影像技术对于基质金属蛋白酶（MMPs）的成像可能有助于检测易破裂的动脉粥样硬化病变。在本研究中，我们开发了一种新型放射性标记化合物，该化合物能够高度选择性地靶向明胶酶MMP亚型（MMP2/9）并具有抑制活性。几种卤素化类似物的抑制活性对于MMP亚型选择性抑制剂（N-苯磺酰亚胺二乙酸单羟肟酸和N-卤代苯氧基苯磺酰亚胺二乙酸单羟肟酸）在纳米摩尔范围内对MMP2/9有效。具有最高抑制活性和选择性的类似物被[123I]标记，产生了中等放射化学产率和高度放射化学纯度。在小鼠中的生物分布研究表明，静脉注射后1小时血液中稳定。静脉注射放射配体并随后对切除的主动脉进行自显影显示，易患动脉粥样硬化的小鼠有示踪剂摄取。放射配体的分布显示出与MMP2/9免疫组织化学染色的共定位。总之，我们开发了一种新型选择性放射性标记的MMP2/9抑制剂，适用于单光子发射计算机断层摄影术（SPECT）成像，能有效靶向小鼠的动脉粥样硬化病变。
• RADIOLABELLED MMP SELECTIVE COMPOUNDS
  申请人：Van Eck-Smit Bertha Louise Frederike

  公开号：US20110171133A1

  公开（公告）日：2011-07-14

  The invention is directed to radiolabelled MMP selective compounds, a processes for the preparation thereof, and uses thereof. The derivatives of the invention have formula (I) wherein Y represents O, CH 2 , (CH 2 ) 2 , S, NH, or C(═O)NH; X represents 1-5 substituents, wherein said substituents can be the same or different and wherein at least one of said substituents comprises a radioisotope suitable for PET and/or SPECT and/or a β-emitter; Z is S; Q is chosen from the group consisting of 3-pyridyl and carboxyl; and R is chosen from the group consisting of C(═O)—NH—OH, (II), (IV). The MMP selective compounds of the invention are selective for MMPs and can be used for the identification and treatment of unstable atherosclerotic plaques.

  该发明涉及放射性标记的MMP选择性化合物，其制备方法和用途。该发明的衍生物具有式（I），其中Y代表O、CH2、（ ）2、S、NH或C（═O）NH；X代表1-5个取代基，其中所述取代基可以相同或不同，且至少一个取代基包括适用于PET和/或SPECT和/或β放射性同位素；Z为S；Q选择自3-吡啶基和羧基的群；R选择自C（═O）—NH—OH，（II），（IV）的群。该发明的MMP选择性化合物对MMP选择性，并可用于不稳定的动脉粥样硬化斑块的识别和治疗。
• Radiolabelled MMP selective compounds
  申请人：Van Eck-Smit Bertha Louise Frederike

  公开号：US08524194B2

  公开（公告）日：2013-09-03

  The invention is directed to radiolabelled MMP selective compounds, a processes for the preparation thereof, and uses thereof. The derivatives of the invention have formula (I) wherein Y represents O, CH2, (CH2)2, S, NH, or C(═O)NH; X represents 1-5 substituents, wherein said substituents can be the same or different and wherein at least one of said substituents comprises a radioisotope suitable for PET and/or SPECT and/or a β-emitter; Z is S; Q is chosen from the group consisting of 3-pyridyl and carboxyl; and R is chosen from the group consisting of C(═O)—NH—OH, (II), (III, (IV). The MMP selective compounds of the invention are selective for MMPs and can be used for the identification and treatment of unstable atherosclerotic plaques.

  本发明涉及放射性标记的MMP选择性化合物，其制备过程和用途。本发明的衍生物具有式（I），其中Y代表O、CH2、（ ）2、S、NH或C（═O）NH；X代表1-5个取代基，其中所述取代基可以相同或不同，且其中至少一个取代基包含适用于PET和/或SPECT和/或β放射性核素的放射性同位素；Z为S；Q选择自3-吡啶基和羧基的群；R选择自C（═O）—NH—OH、（II）、（III）、（IV）的群。本发明的MMP选择性化合物对MMP具有选择性，可用于不稳定的动脉粥样硬化斑块的鉴定和治疗。
• Dual Inhibitors of Matrix Metalloproteinases and Carbonic Anhydrases: Iminodiacetyl-Based Hydroxamate−Benzenesulfonamide Conjugates
  作者：Sérgio M. Marques、Elisa Nuti、Armando Rossello、Claudiu T. Supuran、Tiziano Tuccinardi、Adriano Martinelli、M. Amélia Santos

  DOI：10.1021/jm800964f

  日期：2008.12.25

  Matrix metalloproteinases (MMPs) and carbonic anhydrases (CAs) are two classes of zinc enzymes with different roles and catalytic targets, such as the degradation of most of the extracellular matrix (ECM) proteins and the regulation of the CO2/HCO3- equilibrium in the cells, respectively. Both families have isoforms which were proved to be involved in several stages of carcinogenic processes, and so the selective inhibition of these enzymes might be of interest in cancer therapy. We report herein the design, synthesis, and in vitro evaluation of a series Of Compounds possessing the iminodiacetic acid as the main backbone and two functional groups attached, namely, the hydroxamic acid and the arylsulfonamide (ArSO2NH2) moieties, to enable the inhibition of MMPs and CAs, respectively. These compounds were demonstrated to strongly inhibit both MMPs and CAs, some of them from the nanomolar to subnanomolar range. Furthermore, a docking study for MMPs was reported for the most promising compound in order to investigate its binding interactions with the different MMPs.