2-(2,6-dithioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione | 848827-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(2,6-dithioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione
• CAS: 848827-86-1
• 化学式: C₁₃H₁₀N₂O₂S₂
• 分子量: 290.367
• InChiKey: YIVPAGQZXIJWBX-VIFPVBQESA-N

物化性质

• 沸点：
  454.8±55.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.69
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  49.41
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-(2,6-dithioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione 在 劳森试剂 、 吗啉 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以65%的产率得到2,3-dihydro-3-thioxo-2-(2,6-dithioxo-3-piperidinyl)-1H-isoindol-1-one
  参考文献：
  名称：

  Thiothalidomides:  Novel Isosteric Analogues of Thalidomide with Enhanced TNF-α Inhibitory Activity

  摘要：

  Thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. However, the mechanisms underlying its pharmacological action are still under investigation. In this regard, oral thalidomide is clinically valuable in the treatment of erythema nodosum leprosum (ENL) and mutiple myeloma and effectively reduces tumor necrosis factor-alpha (TNF-alpha) levels and angiogenesis in vivo. This contrasts with its relatively weak effects on TNF-alpha and angiogenesis in in vitro studies and implies that active metabolites contribute to its in vivo pharmacologic action and that specific analogues would be endowed with potent activity. Our focus in the structural modification of thalidomide is toward the discovery of novel isosteric active analogues. In this regard, a series of thiothalidomides and analogues were synthesized and evaluated for their TNF-alpha inhibitory activity against lipopolysacharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), This was combined with a PBMC viability assay to differentiate reductions in TNF-alpha secretion from cellular toxicity. Two isosteric analogues of thalidomide, compounds 15 and 16, that mostly reflect the parent compound, together with the simple structure, dithioglutarimide 19, potently inhibited TNF-a secretion, compared to thalidomide, 1. The mechanism underpinning this most likely is posttranscriptional, as each of these compounds decreased TNF-alpha mRNA stability via its 3'-UTR. The potency of 19 warrants further study and suggests that replacement of the amide carbonyl with a thiocarbonyl may be beneficial for increased TNF-alpha inhibitory action. In addition, an intact phthalimido moiety appeared to be requisite for TNF-alpha inhibitory activity.

  DOI：

  10.1021/jm030152f
• 作为产物：
  描述：

  (-)-沙利度胺 在 劳森试剂 、 吡啶 作用下， 以 甲苯 为溶剂， 反应 36.0h， 生成 2-(2,6-dithioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Thiothalidomides:  Novel Isosteric Analogues of Thalidomide with Enhanced TNF-α Inhibitory Activity

  摘要：

  Thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. However, the mechanisms underlying its pharmacological action are still under investigation. In this regard, oral thalidomide is clinically valuable in the treatment of erythema nodosum leprosum (ENL) and mutiple myeloma and effectively reduces tumor necrosis factor-alpha (TNF-alpha) levels and angiogenesis in vivo. This contrasts with its relatively weak effects on TNF-alpha and angiogenesis in in vitro studies and implies that active metabolites contribute to its in vivo pharmacologic action and that specific analogues would be endowed with potent activity. Our focus in the structural modification of thalidomide is toward the discovery of novel isosteric active analogues. In this regard, a series of thiothalidomides and analogues were synthesized and evaluated for their TNF-alpha inhibitory activity against lipopolysacharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), This was combined with a PBMC viability assay to differentiate reductions in TNF-alpha secretion from cellular toxicity. Two isosteric analogues of thalidomide, compounds 15 and 16, that mostly reflect the parent compound, together with the simple structure, dithioglutarimide 19, potently inhibited TNF-a secretion, compared to thalidomide, 1. The mechanism underpinning this most likely is posttranscriptional, as each of these compounds decreased TNF-alpha mRNA stability via its 3'-UTR. The potency of 19 warrants further study and suggests that replacement of the amide carbonyl with a thiocarbonyl may be beneficial for increased TNF-alpha inhibitory action. In addition, an intact phthalimido moiety appeared to be requisite for TNF-alpha inhibitory activity.

  DOI：

  10.1021/jm030152f