2-(2-((2,6-dichlorophenyl)amino)phenyl)-2-oxoacetic acid | 66156-75-0

• 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: 2-(2-((2,6-dichlorophenyl)amino)phenyl)-2-oxoacetic acid
• 英文别名: 2-(2,6-Dichloranilino)-phenylglyoxylsaeure；2-(2,6-dichloroanilino)phenylglyoxylic acid；2-[2-(2,6-dichloroanilino)phenyl]-2-oxoacetic acid
• CAS: 66156-75-0
• 化学式: C₁₄H₉Cl₂NO₃
• 分子量: 310.136
• InChiKey: PQSLNUKSAGBMGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-((2,6-dichlorophenyl)amino)phenyl)-2-oxoacetic acid 在 sodium methylate 、 一水合肼 作用下， 以 乙二醇甲醚 为溶剂， 生成 diclofenac sodium
  参考文献：
  名称：

  Synthesis and quantitative structure-activity relationships of diclofenac analogs

  摘要：

  The synthesis of a series of 2-anilinophenylacetic acids, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.

  DOI：

  10.1021/jm00171a008
• 作为产物：
  描述：

  2,6-二氯-N-苯基苯胺 在 sodium hydroxide 、 三氯化铝 作用下， 以 乙醇 、 水 、 苯 为溶剂， 反应 22.17h， 生成 2-(2-((2,6-dichlorophenyl)amino)phenyl)-2-oxoacetic acid
  参考文献：
  名称：

  Synthesis and quantitative structure-activity relationships of diclofenac analogs

  摘要：

  The synthesis of a series of 2-anilinophenylacetic acids, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.

  DOI：

  10.1021/jm00171a008

文献信息

• Substituted phenylglycolic acid and its pharmaceutically acceptable
  申请人：Asahi Kasei Kogyo Kabushiki Kaisha

  公开号：US04166128A1

  公开（公告）日：1979-08-28

  Novel substituted phenylglycolic acid represented by the formula ##STR1## AND ITS PHARMACEUTICALLY ACCEPTABLE NON-TOXIC ESTERS AND SALTS HAVE POTENT ANALGESIC, ANTI-INFLAMMATORY AND ANTIPYRETIC ACTIVITIES, A LOW TOXICITY AND A SATISFACTORY THERAPEUTIC INDEX, AND CAN BE FAVORABLY EMPLOYED AS A MEDICINE FOR TREATMENT OF VARIOUS INFLAMMATORY DISEASES SUCH AS ARTHRITIS, COMMON COLD, RHEUMATISM AND LIKE INFLAMMATIONS AND ALSO FOR ANALGESIC AND ANTIPYRETIC PURPOSES. The substituted phenylglycolic acid is prepared by reacting a lower alkyl ester of 2-(2,6-dichloroanilino)phenylglycolic acid with a basic substance, which lower alkyl ester is also a novel compound and can be obtained starting from 1-(2,6-dichlorophenyl)indole-2,3-dione through 2-(2,6-dichloroanilino)phenylglyoxylic acid and, in turn, a lower alkyl ester of 2-(2,6-dichloroanilino)-phenylglyoxylic acid.

  新型的取代苯基乙醇酸，化学式为##STR1##及其药用可接受的无毒酯和盐具有强效的镇痛、抗炎和退热活性，毒性低，治疗指数满意，可作为治疗各种炎症性疾病如关节炎、感冒、风湿病及类似炎症以及镇痛和退热用途的药物。取代苯基乙醇酸是通过将2-(2,6-二氯苯胺基)苯基乙醇酸的较低烷基酯与碱性物质反应制备的，这种较低烷基酯也是一种新型化合物，可以从1-(2,6-二氯苯基)吲哚-2,3-二酮出发，经过2-(2,6-二氯苯胺基)苯甘酸和依次是2-(2,6-二氯苯胺基)苯甘酸较低烷基酯获得。
• Isolation and Structural Characterization of Degradation Products of Aceclofenac by HPLC, HRMS and 2D NMR
  作者：Santhosh Guduru、V.V.S.R.N. Anji Karun Mutha、B. Vijayabhaskar、Muralidharan Kaliyaperumal、Raghu Babu Korupolu、Kishore Babu Bonige、Chidananda Swamy Rumalla

  DOI：10.14233/ajchem.2019.21798

  日期：2019.3

  The stability of aceclofenac under stress conditions was assessed to identify the degradation products. So, it was subjected to stress conditions like acid, base and oxidation, according to ICH guideline Q1A (R2). One degradation product formed when the drug was subjected to acid stress. Three degradation products were formed during the basic stress condition. The drug substance was found to be stable to oxidative stress. The degradants formed during the stress were separated on a C-18 column using gradient preparative HPLC elution. The only product (DP-2) formed during the acid stress and this one is same as of one of the three degradation products (DP-1, DP-2, DP-3) were formed during base stress. 1D and 2D NMR spectra and mass spectral analysis supported the proposed structures for the products. The products DP-2 and DP-3 have been reported earlier but this is the first report of product DP-1 as a degradation product of aceclofenac.

  在应力条件下评估了阿司匹林在应力条件下的稳定性，以确定降解产物。因此，根据ICH指南Q1A（R2），将其置于酸、碱和氧化等应力条件下。当药物置于酸性应力下时，形成了一种降解产物。在碱性应力条件下形成了三种降解产物。药物物质在氧化应力下被发现是稳定的。在应力条件下形成的降解物在C-18柱上使用梯度制备HPLC洗脱分离。在酸性应力下只形成了一个产物（DP-2），这个产物与在碱性应力下形成的三种降解产物（DP-1、DP-2、DP-3）中的一种相同。 1D和2D NMR光谱和质谱分析支持了产品的拟议结构。产品DP-2和DP-3以前已有报道，但这是首次报告DP-1产品作为阿司匹林的降解产物。
• US4166128A
  申请人：——

  公开号：US4166128A

  公开（公告）日：1979-08-28
• Synthesis and quantitative structure-activity relationships of diclofenac analogs
  作者：Peter Moser、Alfred Sallmann、Irmgard Wiesenberg

  DOI：10.1021/jm00171a008

  日期：1990.9

  The synthesis of a series of 2-anilinophenylacetic acids, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.