2-propylpentanoic acid 4-(5-thioxo-5H-1,2-dithiol-3-yl)phenyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 2-propylpentanoic acid 4-(5-thioxo-5H-1,2-dithiol-3-yl)phenyl ester
• 英文别名: 4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl 2-propylpentanoate；5-(p-hydroxyphenyl)-3H-1,2-dithiol-3-thione valproate；[4-(5-Sulfanylidenedithiol-3-yl)phenyl] 2-propylpentanoate
• 化学式: C₁₇H₂₀O₂S₃
• 分子量: 352.543
• InChiKey: WREBYPQOSZWUKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  胆维他 在 4-二甲氨基吡啶 、 吡啶盐酸盐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 24.42h， 生成 2-propylpentanoic acid 4-(5-thioxo-5H-1,2-dithiol-3-yl)phenyl ester
  参考文献：
  名称：

  氨基-ADT 的合成提供了水解稳定的酰胺偶联硫化氢释放药物靶标的途径

  摘要：

  随着硫化氢 (H2S) 的其他生理功能的发现，开发外源 H2S 输送的实用方法非常重要。特别是，正在研究通过酯键与释放 H2S 的茴香脑二硫代硫酮 (ADT-OH) 功能化的非甾体抗炎药 (NSAID) 的联合抗炎和抗氧化潜力。然而，药物和 H2S 输送成分之间连接的化学稳定性是这些化合物中关键且可控的连接。由于酯类容易水解，特别是在口服给药应用中的胃酸等酸性条件下，我们在此报告了氨基-ADT (ADT-NH2 ) 的简单合成，并为药物萘普生和 ADT-NH2 成功衍生化提供了条件。丙戊酸。使用紫外可见光谱和高效液相色谱分析，我们证明酰胺官能化 ADT 衍生物比酯官能化 ADT 衍生物更耐水解。

  DOI：

  10.1055/s-0035-1560603

文献信息

• New nuclear transcription factors regulators
  申请人：CTG Pharma S.r.l.

  公开号：EP1645288A1

  公开（公告）日：2006-04-12

  The present invention relates to novel compounds that are nuclear transcription factors (NTF) regulators. The present invention also provides methods for treating, preventing and/or reducing inflammation-associated diseases by regulating NTF in the cardiovascular, connective tissue, pulmonary, gastrointestinal, respiratory, urogenital, nervous, or cutaneous systems as well as tumoral and infective diseases employing said compounds. The present invention is based on the discovery that it is possible to link regulators of NTF to a pharmacologically active compound helpful for treating disorders in the cardiovascular, connective tissue, pulmonary, gastrointestinal, respiratory, urogenital, nervous, or cutaneous systems or tumoral and infective diseases. The resulting compounds have good bioavailability, increased activity and/or safety.

  本发明涉及一种新型化合物，这些化合物是核转录因子（NTF）调节剂。本发明还提供了通过调节心血管、结缔组织、肺部、胃肠、呼吸、泌尿生殖、神经或皮肤系统以及肿瘤和感染性疾病中的NTF来治疗、预防和/或减少与炎症相关疾病的方法。本发明基于这样的发现：可以将NTF的调节剂与对治疗心血管、结缔组织、肺部、胃肠、呼吸、泌尿生殖、神经或皮肤系统或肿瘤和感染性疾病有帮助的药理活性化合物联系起来。由此产生的化合物具有良好的生物利用度、增强的活性和/或安全性。
• 5-(p-hydroxyphenyl)-3H-1,2-dithiol-3-thione valproate ester
  申请人：Sulfidris S.r.l.

  公开号：EP1886681A3

  公开（公告）日：2008-11-19

  The present invention relates to a nuclear transcription factors (NTF) regulator. The present invention also provides methods for treating, preventing and/or reducing inflammation-associated diseases by regulating NTF in the cardiovascular, connective tissue, pulmonary, gastrointestinal, respiratory, urogenital, nervous, or cutaneous systems as well as tumoral and infective diseases employing said compound.

  本发明涉及一种核转录因子（NTF）调节剂。本发明还提供了通过调节心血管、结缔组织、肺、胃肠、呼吸、泌尿生殖、神经或皮肤系统以及肿瘤和感染性疾病中的 NTF 来治疗、预防和/或减少炎症相关疾病的方法。
• 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
• Synthesis of Amino-ADT Provides Access to Hydrolytically Stable Amide-Coupled Hydrogen Sulfide Releasing Drug Targets
  作者：Michael Pluth、Matthew Hammers、Loveprit Singh、Leticia Montoya、Alan Moghaddam

  DOI：10.1055/s-0035-1560603

  日期：——

  As additional physiological functions of hydrogen sulfide (H2S) are discovered, developing practical methods for exogenous H2S delivery is important. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) functionalized with H2S-releasing anethole dithiolethione (ADT-OH) through ester bonds are being investigated for their combined anti-inflammatory and antioxidant potential. The chemical robustness

  随着硫化氢 (H2S) 的其他生理功能的发现，开发外源 H2S 输送的实用方法非常重要。特别是，正在研究通过酯键与释放 H2S 的茴香脑二硫代硫酮 (ADT-OH) 功能化的非甾体抗炎药 (NSAID) 的联合抗炎和抗氧化潜力。然而，药物和 H2S 输送成分之间连接的化学稳定性是这些化合物中关键且可控的连接。由于酯类容易水解，特别是在口服给药应用中的胃酸等酸性条件下，我们在此报告了氨基-ADT (ADT-NH2 ) 的简单合成，并为药物萘普生和 ADT-NH2 成功衍生化提供了条件。丙戊酸。使用紫外可见光谱和高效液相色谱分析，我们证明酰胺官能化 ADT 衍生物比酯官能化 ADT 衍生物更耐水解。