2-((methylsulfonyl)thio)ethyl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate | 948028-89-5

• 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-((methylsulfonyl)thio)ethyl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate
• 英文别名: [2-(2,6-dichloro-phenylamino)phenyl]acetic acid 2-methanesulfonylsulfanyl-ethyl ester；ACS32；2-Methylsulfonylsulfanylethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate
• CAS: 948028-89-5
• 化学式: C₁₇H₁₇Cl₂NO₄S₂
• 分子量: 434.364
• InChiKey: UEGHCRVBFGDJJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  S-(2-羟基乙基)甲烷硫代磺酸酯 、 双氯芬酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以51.5%的产率得到2-((methylsulfonyl)thio)ethyl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate
  参考文献：
  名称：

  Hydrogen sulphide-releasing diclofenac derivatives inhibit breast cancer-induced osteoclastogenesis in vitro and prevent osteolysis ex vivo

  摘要：

  BACKGROUND AND PURPOSE Hydrogen sulphide (H2S) and prostaglandins are both involved in inflammation, cancer and bone turnover, and non‐steroidal anti‐inflammatory drugs (NSAIDs) and H2S donors exhibit anti‐inflammatory and anti‐tumour properties. H2S‐releasing diclofenac (S‐DCF) derivatives are a novel class of NSAIDs combining the properties of a H2S donor with those of a conventional NSAID.EXPERIMENTAL APPROACH We studied the effects of the S‐DCF derivatives ACS15 and ACS32 on osteoclast and osteoblast differentiation and activity in vitro, human and mouse breast cancer cells support for osteoclast formation and signalling in vitro, and osteolysis ex vivo.KEY RESULTS The S‐diclofenac derivatives ACS15 and ACS32 inhibited the increase in osteoclast formation induced by human MDA‐MB‐231 and MCF‐7 and mouse 4T1 breast cancer cells without affecting breast cancer cell viability. Conditioned media from human MDA‐MB‐231 cells enhanced IκB phosphorylation and osteoclast formation and these effects were significantly inhibited following treatment by ACS15 and ACS32, whereas the parent compound diclofenac had no effects. ACS15 and ACS32 inhibited receptor activator of NFκB ligand‐induced osteoclast formation and resorption, and caused caspase‐3 activation and apoptosis in mature osteoclasts via a mechanism dependent on IKK/NFκB inhibition. In calvaria organ culture, human MDA‐MB‐231 cells caused osteolysis, and this effect was completely prevented following treatment with ACS15 and ACS32.CONCLUSIONS AND IMPLICATIONS S‐diclofenac derivatives inhibit osteoclast formation and activity, suppress breast cancer cell support for osteoclastogenesis and prevent osteolysis. This suggests that H2S‐releasing diclofenac derivatives exhibit anti‐resorptive properties, which might be of clinical value in the treatment of osteolytic bone disease.

  DOI：

  10.1111/j.1476-5381.2011.01704.x

文献信息

• Methanethiosulfonate derivatives as ligands of the STAT3-SH2 domain
  作者：Elena Gabriele、Chiara Ricci、Fiorella Meneghetti、Nicola Ferri、Akira Asai、Anna Sparatore

  DOI：10.1080/14756366.2016.1252757

  日期：2017.1.1

  antiproliferative activity on HCT-116 cancer cell line. These results suggest that methanethiosulfonate moiety can be considered a useful scaffold in the preparation of new direct STAT3 inhibitors. Interestingly, an unusual kind of organo-sulfur derivative, endowed with valuable antiproliferative activity, was occasionally isolated. [Formula: see text].

  为了发现可能用作抗癌药的新型STAT3直接抑制剂，合成了一组甲硫代磺酸盐药物杂化物。体外试验表明，所有的硫代磺酸化合物都能够牢固而有选择地结合STAT3-SH2结构域，而母体药物则完全没有这种能力。另外，它们中的一些对HCT-116癌细胞系显示出中等的抗增殖活性。这些结果表明甲硫代磺酸盐部分可以被认为是制备新的直接STAT3抑制剂的有用支架。有趣的是，偶尔分离出一种具有有价值的抗增殖活性的不寻常的有机硫衍生物。[公式：见文字]。
• Hydrogen sulphide-releasing diclofenac derivatives inhibit breast cancer-induced osteoclastogenesis <i>in vitro</i> and prevent osteolysis <i>ex vivo</i>
  作者：J Frantzias、JG Logan、P Mollat、A Sparatore、P Del Soldato、SH Ralston、AI Idris

  DOI：10.1111/j.1476-5381.2011.01704.x

  日期：2012.3

  BACKGROUND AND PURPOSE Hydrogen sulphide (H2S) and prostaglandins are both involved in inflammation, cancer and bone turnover, and non‐steroidal anti‐inflammatory drugs (NSAIDs) and H2S donors exhibit anti‐inflammatory and anti‐tumour properties. H2S‐releasing diclofenac (S‐DCF) derivatives are a novel class of NSAIDs combining the properties of a H2S donor with those of a conventional NSAID.EXPERIMENTAL APPROACH We studied the effects of the S‐DCF derivatives ACS15 and ACS32 on osteoclast and osteoblast differentiation and activity in vitro, human and mouse breast cancer cells support for osteoclast formation and signalling in vitro, and osteolysis ex vivo.KEY RESULTS The S‐diclofenac derivatives ACS15 and ACS32 inhibited the increase in osteoclast formation induced by human MDA‐MB‐231 and MCF‐7 and mouse 4T1 breast cancer cells without affecting breast cancer cell viability. Conditioned media from human MDA‐MB‐231 cells enhanced IκB phosphorylation and osteoclast formation and these effects were significantly inhibited following treatment by ACS15 and ACS32, whereas the parent compound diclofenac had no effects. ACS15 and ACS32 inhibited receptor activator of NFκB ligand‐induced osteoclast formation and resorption, and caused caspase‐3 activation and apoptosis in mature osteoclasts via a mechanism dependent on IKK/NFκB inhibition. In calvaria organ culture, human MDA‐MB‐231 cells caused osteolysis, and this effect was completely prevented following treatment with ACS15 and ACS32.CONCLUSIONS AND IMPLICATIONS S‐diclofenac derivatives inhibit osteoclast formation and activity, suppress breast cancer cell support for osteoclastogenesis and prevent osteolysis. This suggests that H2S‐releasing diclofenac derivatives exhibit anti‐resorptive properties, which might be of clinical value in the treatment of osteolytic bone disease.