[2-(2,6-dichloroanilino)phenyl]acetate diethylene glycol | 108914-03-0

• 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-(2,6-dichloroanilino)phenyl]acetate diethylene glycol
• 英文别名: diclofenac；2'-{2-[(2,6-dichlorophenyl)-amino]-phenyl-acetoxy}-2-hydroxy-diethyloxide；2-(2-Hydroxyethoxy)ethyl 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetate；2-(2-hydroxyethoxy)ethyl {2-[(2,6-dichlorophenyl)amino]phenyl} acetate；2-(2-Hydroxyethoxy)ethyl {2-[(2,6-dichlorophenyl)amino]phenyl}acetate；2-(2-hydroxyethoxy)ethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate
• CAS: 108914-03-0
• 化学式: C₁₈H₁₉Cl₂NO₄
• 分子量: 384.259
• InChiKey: TYJGETBDTFVKAB-UHFFFAOYSA-N

物化性质

• 沸点：
  506.1±50.0 °C(Predicted)
• 密度：
  1.345±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲基磺酰氯 、 [2-(2,6-dichloroanilino)phenyl]acetate diethylene glycol 在 N-甲基吗啉 、 硫酸 作用下， 以 水 为溶剂， 反应 5.98h， 以86.3%的产率得到2-{2-[(methylsulfonyl)oxy]ethoxy}ethyl {2-[(2,6-dichlorophenyl)amino]phenyl} acetate
  参考文献：
  名称：

  [EN] MANUFACTURING PROCESS FOR NO-DONATING COMPOUNDS SUCH AS NO-DONATING DICLOFENAC
  [FR] PROCEDE DE FABRICATION DE COMPOSES DONNEURS DE NO TELS QUE DU DICLOFENAC DONNEUR DE NO

  摘要：

  本发明涉及一种利用磺化中间体制备NO供体化合物的新工艺。该发明涉及其中制备的新中间体，适用于大规模制造NO供体化合物。该发明还涉及利用新中间体制造药用活性NO供体化合物。该发明还涉及NO供体NSAIDs的实质晶体形式，特别是2-[2-(硝基氧基)乙氧基]乙基{2-[(2,6-二氯苯基)氨基]苯基}醋酸酯，其制备以及含有所述晶体形式的药物配方，以及利用所述晶体形式制备药物的用途。

  公开号：

  WO2004026808A1
• 作为产物：
  描述：

  双氯芬酸 、 二乙二醇 在 N,N'-羰基二咪唑 作用下， 以 氯仿 为溶剂， 反应 28.0h， 以78%的产率得到[2-(2,6-dichloroanilino)phenyl]acetate diethylene glycol
  参考文献：
  名称：

  聚氧乙烯酯作为酮洛芬，萘普生和双氯芬酸的皮肤前药的体外和体内评价。

  摘要：

  合成了酮洛芬（1（ae）），萘普生（2（ae））和双氯芬酸（3（ae））的新型聚氧乙烯酯，并将其评价为萘普生，酮洛芬和双氯芬酸的潜在皮肤前药。这些酯是通过琥珀酸间隔基使这些药物与聚氧乙二醇偶联而获得的。在缓冲溶液和猪酯酶中测定酯1（ae），2（ae）和3（ae）的水溶解度，亲脂性和水解速率。在体外研究了这些前药通过切除的人皮肤的渗透性。此外，我们研究了酯1（d），酯2（e）和酯3（e）的体内局部抗炎活性，它们具有最佳的体外分布，评估了这些化合物抑制烟酸甲酯（MN）的能力。在健康的人类志愿者身上引起皮肤红斑。酯1（ae），2（ae）和3（ae）显示出良好的水稳定性和快速的酶促裂解，并且它们的水解速率，无论是化学的还是酶促的，都不受用作促成性的聚氧乙烯链的长度的显着影响。关于体外经皮吸收研究，与它们各自的母体药物相比，只有酯1（de），2（de）和3（ce）表现出通过角质层和表皮膜的通量增加。

  DOI：

  10.1016/s0928-0987(01)00163-4

文献信息

• Esters and amides containing the
  申请人：Dr. Karl Thomae GmbH

  公开号：US04362738A1

  公开（公告）日：1982-12-07

  Compounds of the formula ##STR1## wherein each X, which may be identical or different from the other X, is oxygen or imino; R.sub.1 is hydrogen, fluorine, chlorine or bromine; R.sub.2 and R.sub.3, which may be identical or different from each other, are each hydrogen; unsubstituted or mono-substituted alkyl of 1 to 6 carbon atoms, where the substituent is phenyl or dialkylamino with 1 to 3 carbon atoms in each alkyl moiety; pyridyl; or cycloalkyl of 5 to 7 carbon atoms; R.sub.2 and R.sub.3, together with each other and the nitrogen atoms to which they are attached, are pyrrolidino, piperidino, hexamethyleneimino, morpholino, N-aryl-piperazino or N-(alkyl of 1 to 3 carbon atoms)-piperazino; A is cycloalkylene of 5 to 7 carbon atoms; unsubstituted or substituted alkylene of 2 to 10 carbon atoms, where the substituents are one to two alkyls of 1 to 3 carbon atoms each, one to two carbalkoxys of 2 to 4 carbon atoms each, one to two phenyls, one to four hydroxyls, one halomethyl, one hydroxymethyl, one alkanoyloxy of 1 to 18 carbon atoms, one alkanoyloxymethyl of 1 to 18 carbon atoms in the alkanoyl moiety or one ##STR2## where R.sub.1, R.sub.2 and R.sub.3 have the meanings previously defined; or alkylene of 2 to 10 carbon atoms interrupted by oxygen, sulfur, sulfoxide, sulfonyl, phenyl, cyclohexyl, pyridyl, piperazino or unsubstituted or substituted imino, where the substituent on the imino group is alkyl of 1 to 6 carbon atoms, phenyl or phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety; B is the acyl residue of an antiphlogistic carboxylic acid; and their non-toxic, pharmacologically acceptable acid addition salts. The compounds as well as their salts are useful as anti-inflammatories.

  公式##STR1##的化合物，其中每个X可以相同也可以不同于其他X，是氧或亚胺；R.sub.1是氢，氟，氯或溴；R.sub.2和R.sub.3，可以相同也可以相互不同，都是氢；未取代或单取代的1到6碳原子的烷基，其中取代基是苯基或1到3碳原子的二烷基氨基；吡啶基；或5到7碳原子的环烷基；R.sub.2和R.sub.3，与彼此以及它们所连接的氮原子一起，是吡咯烷基，哌啶基，己亚胺基，吗啉基，N-芳基哌嗪基或N-(1到3碳原子的烷基)哌嗪基；A是5到7碳原子的环烷基；未取代或取代的2到10碳原子的亚烷基，其中取代基是一到两个每个含有1到3碳原子的烷基，一到两个每个含有2到4碳原子的碳烷氧基，一到两个苯基，一到四个羟基，一个卤甲基，一个羟甲基，一个1到18碳原子的烷酰氧基，一个在烷酰基部分含有1到18碳原子的烷酰氧甲基或一个##STR2##其中R.sub.1，R.sub.2和R.sub.3具有先前定义的含义；或2到10碳原子的亚烷基，通过氧，硫，亚砜，磺酰基，苯基，环己基，吡啶基，哌嗪基或未取代或取代的亚胺基中断，其中亚胺基上的取代基是1到6碳原子的烷基，苯基或1到3碳原子的苯烷基；B是一种抗炎的羧酸的酰基残基；以及它们的非毒性，药理学上可接受的酸加成盐。这些化合物以及它们的盐可以用作抗炎药。
• Nitrosated and nitrosylated nonsteroidal antiinflammatory compounds, compositons and methods of use
  申请人：——

  公开号：US20020016322A1

  公开（公告）日：2002-02-07

  The present invention describes novel nitrosated and/or nitrosylated nonsteroidal antiinflammatory compounds, and novel compositions comprising at least one nitrosated and/or nitrosylated nonsteroidal antiinflammatory compound, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase. The present invention also provides methods for treating, preventing and/or reducing inflammation, pain, and fever; decreasing or reversing the gastrointestinal, renal and other toxicities resulting from the use of nonsteroidal antiinflammatory drugs; treating and/or preventing gastrointestinal disorders; treating inflammatory disease states and disorders; and treating and/or preventing ophthalmic diseases or disorders.

  本发明描述了新型的亚硝酸化和/或亚硝基化的非甾体抗炎化合物，以及包含至少一种亚硝酸化和/或亚硝基化的非甾体抗炎化合物的新型组合物，以及可选地含有至少一种捐赠、转移或释放一氧化氮、提高内皮源性松弛因子内源水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物的化合物。本发明还提供了治疗、预防和/或减轻炎症、疼痛和发热的方法；减少或逆转由非甾体抗炎药物使用引起的胃肠道、肾脏和其他毒性；治疗和/或预防胃肠道疾病；治疗炎症性疾病和疾病状态；以及治疗和/或预防眼科疾病或疾病状态。
• Nitrosated and nitrosylated nonsteroidal antiinflammatory compounds, compositions and methods of use
  申请人：——

  公开号：US20030207919A1

  公开（公告）日：2003-11-06

  The present invention describes novel nitrosated and/or nitrosylated nonsteroidal antiinflammatory compounds, and novel compositions comprising at least one nitrosated and/or nitrosylated nonsteroidal antiinflammatory compound, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase. The present invention also provides methods for treating, preventing and/or reducing inflammation, pain, and fever; decreasing or reversing the gastrointestinal, renal and other toxicities resulting from the use of nonsteroidal antiinflammatory drugs; treating and/or preventing gastrointestinal disorders; treating inflammatory disease states and disorders; and treating and/or preventing ophthalmic diseases or disorders.

  本发明描述了新型的亚硝酸化和/或亚硝基化非甾体抗炎化合物，以及至少包含一种亚硝酸化和/或亚硝基化非甾体抗炎化合物以及可选地至少一种捐赠、转移或释放一氧化氮、提高内皮源性松弛因子内源水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物的化合物的新型组合物。本发明还提供了治疗、预防和/或减轻炎症、疼痛和发热的方法；减少或逆转非甾体抗炎药物使用所导致的胃肠道、肾脏和其他毒性；治疗和/或预防胃肠道疾病；治疗炎症性疾病状态和疾病；以及治疗和/或预防眼科疾病或疾病的方法。
• ELECTRIC MOTOR
  申请人：Atarashi Hirofumi

  公开号：US20090096314A1

  公开（公告）日：2009-04-16

  The present invention relates to a new process for the preparation of NO-donating compounds using a sulfonated intermediate. The invention relates to new intermediates prepared therein suitable for large scale manufacturing of NO-donating compounds. The invention further relates to the use of the new intermediates for the manufacturing of pharmaceutically active NO-donating compounds. The invention further relates to a substantially crystalline form of NO-donating NSAIDs, especially 2-[2-(nitrooxy)ethoxy]ethyl 2-[(2,6-dichlorophenyl)amino]phenyl}acetate, the preparation thereof and to pharmaceutical formulations containing said crystalline form and to the use of said crystalline form in the preparation of a medicament.

  本发明涉及一种利用磺化中间体制备NO供体化合物的新工艺。该发明涉及其中制备的新中间体，适用于大规模制造NO供体化合物。该发明进一步涉及利用新中间体制造药用活性NO供体化合物。该发明还涉及NO供体NSAIDs的实质晶态形式，特别是2-[2-(硝基氧基)乙氧基]乙基2-[(2,6-二氯苯基)氨基]苯基}乙酸酯及其制备，以及含有该晶态形式的制药配方和在制备药物时使用该晶态形式。
• N-PHENYL ANTHRANILIC ACID DERIVATIVES AND USES THEREOF
  申请人：Attali Bernard

  公开号：US20100137296A1

  公开（公告）日：2010-06-03

  Compounds that can be used as openers or blockers of voltage-dependent potassium channels, and which are useful in the treatment of conditions such as central or peripheral nervous system disorders through the modulation of potassium ion flux through voltage-dependent potassium channels and/or depressing or enhancing cortical and/or peripheral neuron activity, compositions containing same and methods utilizing same are disclosed. Also disclosed are modulators of voltage-dependent potassium channels, which exhibit blocking of a TRPV1 channel, and hence are useful in the treatment of TRPV1-related conditions.

  本发明揭示了可以用作电压依赖性钾离子通道的开放剂或阻断剂的化合物，其通过调节电压依赖性钾离子通道中的钾离子通量和/或抑制或增强皮质和/或外周神经元活动，在治疗中枢或外周神经系统疾病方面具有用途，以及包含该化合物的组合物和利用该化合物的方法。此外，本发明还揭示了电压依赖性钾离子通道的调节剂，其表现出对TRPV1通道的阻断作用，因此在治疗TRPV1相关疾病方面具有用途。