2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole-3-thione-5-yl)phenyl ester | 912758-00-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole-3-thione-5-yl)phenyl ester
• 英文别名: S-diclofenac；[4-(5-sulfanylidenedithiol-3-yl)phenyl] 2-[2-(2,6-dichloroanilino)phenyl]acetate
• CAS: 912758-00-0
• 化学式: C₂₃H₁₅Cl₂NO₂S₃
• 分子量: 504.482
• InChiKey: BRDUXOHVEZVAHI-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO 中≤10mg/ml；二甲基甲酰胺中 10mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 储存条件：
  -20°C，密闭保存，确保干燥。

制备方法与用途

S-双氯芬酸是一种兼具H2S供体特性和非甾体抗炎药（NSAID）功能的混合分子。虽然它能够显著抑制前列腺素的合成，但仍能有效减少对胃黏膜的损害。

反应信息

• 作为产物：
  描述：

  5-(4-羟基-苯基)-[1,2]二硫醇-3-硫酮 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以74%的产率得到2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole-3-thione-5-yl)phenyl ester
  参考文献：
  名称：

  HYDROGEN SULFIDE DERIVATIVES OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

  摘要：

  本发明涉及具有改善的抗炎性质的非甾体抗炎药（NSAIDs）衍生物，用于治疗炎症、疼痛和发热。更具体地说，非甾体抗炎药与释放硫化氢（H2S）的基团结合，以产生具有减少副作用的新的抗炎化合物。

  公开号：

  US20080004245A1
• 作为试剂：
  描述：

  双氯芬酸 、 4-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 5-(4-羟基-苯基)-[1,2]二硫醇-3-硫酮 在 Brine 、 magnesium sulfate 、 methanol-dichloromethane 、 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole-3-thione-5-yl)phenyl ester 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 反应 5.0h， 以was obtained (1.1 g, 74% yield)的产率得到2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole-3-thione-5-yl)phenyl ester
  参考文献：
  名称：

  Hydrogen sulfide derivatives of non-steroidal anti-inflammatory drugs

  摘要：

  本发明涉及非甾体抗炎药（NSAIDs）的衍生物，具有改善的抗炎性能，可用于治疗炎症，疼痛和发热。更具体地说，NSAIDs与释放氢硫化物（H2S）的基团进行衍生，以产生具有减少副作用的新型抗炎化合物。

  公开号：

  US08541398B2

文献信息

• ANTI-INFLAMMATORY COMPOUNDS
  申请人：Sparatore Anna

  公开号：US20090281093A1

  公开（公告）日：2009-11-12

  The present invention relates to novel non steroidal anti-inflammatory compounds (NSAIDs) that release hydrogen sulfide (H 2 S). The present invention also provides methods for treating, preventing and/or reducing inflammation-associated diseases by releasing H 2 S in the cardiovascular, connective tissue, pulmonary, gastrointestinal, respiratory, urogenital, nervous, or cutaneous systems as well as infective diseases employing said compounds.

  本发明涉及新型非甾体抗炎化合物（NSAIDs），它们可以释放硫化氢（H2S）。本发明还提供了通过在心血管、结缔组织、肺、胃肠、呼吸、泌尿生殖、神经或皮肤系统中释放H2S以及使用所述化合物治疗、预防和/或减少与炎症相关的疾病的方法，包括感染性疾病。
• Methods for treatment of sleep-related breathing disorders
  申请人：Snyder Solomon H.

  公开号：US10688096B2

  公开（公告）日：2020-06-23

  Described herein are methods for modulation of the activity of the carotid body that afford therapeutic benefit for sleep-related breathing disorders and related conditions.

  本文描述的是调节颈动脉体活动的方法，可为睡眠相关呼吸紊乱和相关疾病提供治疗益处。
• WO2006/111791
  申请人：——

  公开号：——

  公开（公告）日：——
• Modulation of angiogenesis by dithiolethione-modified NSAIDs and valproic acid
  作者：J S Isenberg、Y Jia、L Field、L A Ridnour、A Sparatore、P Del Soldato、A L Sowers、G C Yeh、T W Moody、D A Wink、R Ramchandran、D D Roberts

  DOI：10.1038/sj.bjp.0707198

  日期：2007.5

  Background and purpose:Angiogenesis involves multiple signaling pathways that must be considered when developing agents to modulate pathological angiogenesis. Because both cyclooxygenase inhibitors and dithioles have demonstrated anti‐angiogenic properties, we investigated the activities of a new class of anti‐inflammatory drugs containing dithiolethione moieties (S‐NSAIDs) and S‐valproate.Experimental approach:Anti‐angiogenic activities of S‐NSAIDS, S‐valproate, and the respective parent compounds were assessed using umbilical vein endothelial cells, muscle and tumor tissue explant angiogenesis assays, and developmental angiogenesis in Fli:EGFP transgenic zebrafish embryos.Key results:Dithiolethione derivatives of diclofenac, valproate, and sulindac inhibited endothelial cell proliferation and induced Ser78 phosphorylation of hsp27, a known molecular target of anti‐angiogenic signaling. The parent drugs lacked this activity, but dithiolethiones were active at comparable concentrations. Although dithiolethiones can potentially release hydrogen sulphide, NaSH did not reproduce some activities of the S‐NSAIDs, indicating that the dithioles regulate angiogenesis through mechanisms other than release of H2S. In contrast to the parent drugs, S‐NSAIDs, S‐valproate, NaSH, and dithiolethiones were potent inhibitors of angiogenic responses in muscle and HT29 tumor explants assessed by 3‐dimensional collagen matrix assays. Dithiolethiones and valproic acid were also potent inhibitors of developmental angiogenesis in zebrafish embryos, but the S‐NSAIDs, remarkably, lacked this activity.Conclusions and implication:S‐NSAIDs and S‐valproate have potent anti‐angiogenic activities mediated by their dithiole moieties. The novel properties of S‐NSAIDs and S‐valproate to inhibit pathological versus developmental angiogenesis suggest that these agents may have a role in cancer treatment.British Journal of Pharmacology (2007) 151, 142–151. doi:10.1038/sj.bjp.0707198
• METHODS FOR TREATMENT OF SLEEP-RELATED BREATHING DISORDERS
  申请人：Snyder Solomon H.

  公开号：US20130131028A1

  公开（公告）日：2013-05-23

  Described herein are methods for modulation of the activity of the carotid body that afford therapeutic benefit for sleep-related breathing disorders and related conditions.