2-(2-(4-bromophenylthio)phenyl)acetic acid | 13420-80-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(2-(4-bromophenylthio)phenyl)acetic acid
• 英文别名: 2-[2-(4-Bromophenyl)sulfanylphenyl]acetic acid
• CAS: 13420-80-9
• 化学式: C₁₄H₁₁BrO₂S
• 分子量: 323.21
• InChiKey: MQFOPIMPCJEXDU-UHFFFAOYSA-N

物化性质

• 熔点：
  124-125 °C
• 沸点：
  449.2±35.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-(4-bromophenylthio)phenyl)acetic acid 在 potassium phosphate 、 四(三苯基膦)钯 、 oxone||potassium monopersulfate triple salt 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 28.0h， 生成 tert-butyl 2-(2-(4'-(2-fluoroacetamido)biphenyl-4-ylsulfonyl)phenyl)acetate
  参考文献：
  名称：

  Synthesis and Preliminary Evaluation in Tumor Bearing Mice of New ¹⁸F-Labeled Arylsulfone Matrix Metalloproteinase Inhibitors as Tracers for Positron Emission Tomography

  摘要：

  New fluorinated, arylsulfone-based matrix metalloproteinase (MMP) inhibitors containing carboxylate as the zinc binding group were synthesized as radiotracers for positron emission tomography. Inhibitors were characterized by K-i for MMP-2 in the nanomolar range and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14. Two of these compounds were obtained in the F-18-radiolabeled form, with radiochemical purity and yield suitable for preliminary studies in mice xenografted with a human U-87 MG glioblastoma. Target density in xenografts was assessed by Western blot, yielding B-max/K-d = 14. The biodistribution of the tracer was dominated by liver uptake and hepatobiliary clearance. Tumor uptake of F-18-labeled MMP inhibitors was about 30% that of [F-18]fluorodeoxyglucose. Accumulation of radioactivity within the tumor periphery colocalized with MMP-2 activity (evaluated by in situ zimography). However, specific tumor uptake accounted for only 18% of total uptake. The aspecific uptake was ascribed to the high binding affinity between the radiotracer and serum albumin.

  DOI：

  10.1021/jm4001743
• 作为产物：
  描述：

  2-碘苯乙酸 、 4-溴苯硫酚 在 铜 、 potassium hydroxide 作用下， 以 水 为溶剂， 100.0 ℃ 、689.49 kPa 条件下， 以94%的产率得到2-(2-(4-bromophenylthio)phenyl)acetic acid
  参考文献：
  名称：

  THIOARYL SUBSTITUTED INHIBITORS OF ZINC PROTEASES AND THEIR USE

  摘要：

  描述了具有下面一般式（I）的化合物及其药学上可接受的盐，其中E、X、m、q、R1、R2、n和ZBG的含义如描述中所述，在治疗中作为锌金属蛋白酶的抑制剂。

  公开号：

  US20090239829A1
• 作为试剂：
  描述：

  2-碘苯乙酸 在 potassium phosphate 、 四(三苯基膦)钯 、 oxone||potassium monopersulfate triple salt 、 2-(2-(4-bromophenylthio)phenyl)acetic acid 、 铜 、 N,N-二异丙基乙胺 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 20.0~140.0 ℃ 、689.49 kPa 条件下， 反应 28.57h， 生成 [¹⁸F]-2-(2-(4'-(2-fluoroacetamido)biphenyl-4-ylsulfonyl)phenyl)acetic acid
  参考文献：
  名称：

  Synthesis and Preliminary Evaluation in Tumor Bearing Mice of New ¹⁸F-Labeled Arylsulfone Matrix Metalloproteinase Inhibitors as Tracers for Positron Emission Tomography

  摘要：

  New fluorinated, arylsulfone-based matrix metalloproteinase (MMP) inhibitors containing carboxylate as the zinc binding group were synthesized as radiotracers for positron emission tomography. Inhibitors were characterized by K-i for MMP-2 in the nanomolar range and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14. Two of these compounds were obtained in the F-18-radiolabeled form, with radiochemical purity and yield suitable for preliminary studies in mice xenografted with a human U-87 MG glioblastoma. Target density in xenografts was assessed by Western blot, yielding B-max/K-d = 14. The biodistribution of the tracer was dominated by liver uptake and hepatobiliary clearance. Tumor uptake of F-18-labeled MMP inhibitors was about 30% that of [F-18]fluorodeoxyglucose. Accumulation of radioactivity within the tumor periphery colocalized with MMP-2 activity (evaluated by in situ zimography). However, specific tumor uptake accounted for only 18% of total uptake. The aspecific uptake was ascribed to the high binding affinity between the radiotracer and serum albumin.

  DOI：

  10.1021/jm4001743

文献信息

• THIOARYL SUBSTITUTED INHIBITORS OF ZINC PROTEASES AND THEIR USE
  申请人：Rossello Armando

  公开号：US20090239829A1

  公开（公告）日：2009-09-24

  There are described compounds having the general formula (I) below and their pharmaceutically acceptable salts thereof, wherein E, X, m, q, R 1 , R 2 , n and ZBG have the meanings reported in the description useful, in therapy, as inhibitors of zinc metalloproteinases.

  描述了具有下面一般式（I）的化合物及其药学上可接受的盐，其中E、X、m、q、R1、R2、n和ZBG的含义如描述中所述，在治疗中作为锌金属蛋白酶的抑制剂。
• Development of Thioaryl-Based Matrix Metalloproteinase-12 Inhibitors with Alternative Zinc-Binding Groups: Synthesis, Potentiometric, NMR, and Crystallographic Studies
  作者：Elisa Nuti、Doretta Cuffaro、Elisa Bernardini、Caterina Camodeca、Laura Panelli、Sílvia Chaves、Lidia Ciccone、Livia Tepshi、Laura Vera、Elisabetta Orlandini、Susanna Nencetti、Enrico A. Stura、M. Amélia Santos、Vincent Dive、Armando Rossello

  DOI：10.1021/acs.jmedchem.8b00096

  日期：2018.5.24

  MMP-12. In the newly synthesized thioaryl derivatives, the nature of the zinc binding group (ZBG) and the sulfur oxidation state were changed. Biological assays carried out in vitro on human MMPs with the resulting compounds led to identification of a sulfide, 4a, bearing an N-1-hydroxypiperidine-2,6-dione (HPD) group as new ZBG. Compound 4a is a promising hit compound since it displayed a nanomolar affinity

  基质金属蛋白酶12（MMP-12）选择性抑制剂可在治疗肺部炎症和心血管疾病中发挥作用。在本研究中，对以前报道的基于4-甲氧基联苯磺酰基异羟肟酸酯和羧酸盐的抑制剂（1b和2b）进行了修饰，以增强其对MMP-12的选择性。在新合成的硫代芳基衍生物中，锌结合基团（ZBG）的性质和硫的氧化态发生了变化。在体外对人MMP进行的生物学分析表明，所得化合物可鉴定带有N -1-羟基哌啶2,6-二酮（HPD）基团的硫化物4a作为新的ZBG。化合物4a是一种有前途的命中化合物，因为它对MMP-12具有纳摩尔浓度的亲和力，对MMP-9，MMP-1和MMP-14具有明显的选择性。进行了Zn 2+溶液络合研究，以表征新化合物的螯合能力，并确认了HPD衍生物的双齿结合模式。X射线晶体学研究使用MMP-12和MMP-9催化域进行了合理化的生物学结果。
• Exploring the Neuroleptic Substituent in Octoclothepin: Potential Ligands for Positron Emission Tomography with Subnanomolar Affinity for α₁-Adrenoceptors
  作者：Jesper L. Kristensen、Ask Püschl、Martin Jensen、Rune Risgaard、Claus T. Christoffersen、Benny Bang-Andersen、Thomas Balle

  DOI：10.1021/jm100652h

  日期：2010.10.14

  A series of 1-(10.11-dihydrodthenzo[b,f]thiepin-(10-y-l)-4-methylpiperazine analogues substituted in the 8-position of the 10,11-dihydrodibenzo[b,f]thiepine scaffold with aryl, heteroaryl. amine, and amide substituents are described. The compounds were: designed using the previously reported Liljefors-Bogeso pharmacophore model for dopamine 1)2 and alpha(1)-adrenocetor antagonists. with the aim of obtaining selective alpha(1)-adrenoceptors antagonists suitable for development as radioligands for imaging of central alpha(1)-adrenoceptors by positron emission tomography. Sixteen aryl and heteroaryl substituted octoclothepin analogues were prepared by a convergent synthesis via coupling of 1-methyl-4-(8-(4,4.5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-10,11-dihydrodibenzo[b,f]thiepin-10yl-piperazine with aryl and heteroaryl halides under palladium catalysis. The most selective compound obtained, (S)-N-(11-(4-methylpiperazin- -yl)-10,11-dihydrodibenzo[b,f]thiepin-2-yl)methyl)isobutyramide (S)-35, showed a similar subnanomolar affinity compared to alpha(1a), alpha(1b,) and alpha(1d)-adrenoceptors and a selectivity ratio of 20, 440, and 20 with respect to D-2, 5-HT2C, and H-1 receptors. respectively.
• WO2008/15139
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, Biological Evaluation, and NMR Studies of a New Series of Arylsulfones As Selective and Potent Matrix Metalloproteinase-12 Inhibitors
  作者：Elisa Nuti、Laura Panelli、Francesca Casalini、Stanislava I. Avramova、Elisabetta Orlandini、Salvatore Santamaria、Susanna Nencetti、Tiziano Tuccinardi、Adriano Martinelli、Giovanni Cercignani、Nicola D’Amelio、Alessandro Maiocchi、Fulvio Uggeri、Armando Rossello

  DOI：10.1021/jm900335a

  日期：2009.10.22

  Overexpression of macrophage-elastase (MMP-12), a member of the matrix metalloproteinases family, can be linked to tissue remodeling and degradation in some inflammatory processes, such as chronic obstructive pulmonary disease (COPD), emphysema, rheumatoid arthritis (RA), and atherosclerosis. On this basis, MMP-12 can be considered an attractive target for studying selective inhibitors that are useful in the development of new therapies for COPD and other inflammatory diseases. We report herein the design, synthesis, and in vitro evaluation of a new series of compounds, possessing an arylsulfonyl scaffold, for their potential as selective inhibitors of MMP-12. The best compound in the series showed an IC50 value of 0.2 nM, with good selectivity over MMP-1 and MMP-14. A docking study was carried out on this compound in order to investigate its binding interactions with MMP-12, and NMR studies on the complex with the MMP-12 catalytic domain were able to validate the proposed binding mode.