2-(tert-butyldimethylsilyloxy)-3-(dodecyloxy)propanethioamide | 1621518-01-1

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 2-(tert-butyldimethylsilyloxy)-3-(dodecyloxy)propanethioamide
• 英文别名: 2-[Tert-butyl(dimethyl)silyl]oxy-3-dodecoxypropanethioamide；2-[tert-butyl(dimethyl)silyl]oxy-3-dodecoxypropanethioamide
• CAS: 1621518-01-1
• 化学式: C₂₁H₄₅NO₂SSi
• 分子量: 403.745
• InChiKey: MSOIXAAFGPTBQY-UHFFFAOYSA-N

物化性质

• 沸点：
  444.9±55.0 °C(predicted)
• 密度：
  0.933±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  26
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  76.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(tert-butyldimethylsilyloxy)-3-(dodecyloxy)propanethioamide 在 硫酸 、 戴斯-马丁氧化剂 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 ethyl 2-(2-(dodecyloxy)acetyl)thiazole-4-carboxylate
  参考文献：
  名称：

  Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

  摘要：

  Group WA cytosolic phospholipase A(2) (GIVA cPLA(2)) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA(2), exhibiting an X-I(50) value of 0.011 mole fraction in a mixed micelle assay and an IC50 of 300 nM in a vesicle assay. In a cellular assay using SW982 fibroblast-like synoviocytes, it suppressed the release of arachidonic acid with an IC50 value of 0.6 mu M. In a prophylactic collagen-induced arthritis model, it exhibited an anti-inflammatory effect comparable to the reference drug methotrexate, whereas in a therapeutic model, it showed results comparable to those of the reference drug Enbrel. In both models, it significantly reduced plasma PGE(2) levels.

  DOI：

  10.1021/jm500192s
• 作为产物：
  描述：

  乙二醇单十二烷基醚 在 18-冠醚-6 、 (4-CH₃OC₆H₄P(O)-S-)2 、 双氧水 、 四丁基硫酸氢铵 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 0.5h， 生成 2-(tert-butyldimethylsilyloxy)-3-(dodecyloxy)propanethioamide
  参考文献：
  名称：

  Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo

  摘要：

  Group WA cytosolic phospholipase A(2) (GIVA cPLA(2)) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA(2), exhibiting an X-I(50) value of 0.011 mole fraction in a mixed micelle assay and an IC50 of 300 nM in a vesicle assay. In a cellular assay using SW982 fibroblast-like synoviocytes, it suppressed the release of arachidonic acid with an IC50 value of 0.6 mu M. In a prophylactic collagen-induced arthritis model, it exhibited an anti-inflammatory effect comparable to the reference drug methotrexate, whereas in a therapeutic model, it showed results comparable to those of the reference drug Enbrel. In both models, it significantly reduced plasma PGE(2) levels.

  DOI：

  10.1021/jm500192s

文献信息

• Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo
  作者：George Kokotos、Astrid J. Feuerherm、Efrosini Barbayianni、Ishita Shah、Mari Sæther、Victoria Magrioti、Thuy Nguyen、Violetta Constantinou-Kokotou、Edward A. Dennis、Berit Johansen

  DOI：10.1021/jm500192s

  日期：2014.9.25

  Group WA cytosolic phospholipase A(2) (GIVA cPLA(2)) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA(2), exhibiting an X-I(50) value of 0.011 mole fraction in a mixed micelle assay and an IC50 of 300 nM in a vesicle assay. In a cellular assay using SW982 fibroblast-like synoviocytes, it suppressed the release of arachidonic acid with an IC50 value of 0.6 mu M. In a prophylactic collagen-induced arthritis model, it exhibited an anti-inflammatory effect comparable to the reference drug methotrexate, whereas in a therapeutic model, it showed results comparable to those of the reference drug Enbrel. In both models, it significantly reduced plasma PGE(2) levels.