6,6-dimethyl-4-(2-(propan-2-ylidene)hydrazinyl)-6,7-dihydro-2H-indazole-3(5H)-thione | 1374976-90-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: 6,6-dimethyl-4-(2-(propan-2-ylidene)hydrazinyl)-6,7-dihydro-2H-indazole-3(5H)-thione
• 英文别名: 6,6-dimethyl-4-(2-propan-2-ylidenehydrazinyl)-5,7-dihydro-2H-indazole-3-thione
• CAS: 1374976-90-5
• 化学式: C₁₂H₁₈N₄S
• 分子量: 250.368
• InChiKey: WOZGGVCESXVFEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  48.78
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  3-(2,4-Dichloro-phenylamino)-5,5-dimethyl-cyclohex-2-enone 在 一水合肼 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 二甲基亚砜 为溶剂， 反应 30.83h， 生成 6,6-dimethyl-4-(2-(propan-2-ylidene)hydrazinyl)-6,7-dihydro-2H-indazole-3(5H)-thione
  参考文献：
  名称：

  Synthesis, biological evaluation, and molecular docking studies of benzyl, alkyl and glycosyl [2-(arylamino)-4,4-dimethyl-6-oxo-cyclohex-1-ene]carbodithioates, as potential immunomodulatory and immunosuppressive agents

  摘要：

  The immunomodulating properties of functionalized [2-(arylamino)-4,4-dimethyl-6-oxo-cyclohex-1-ene] carbodithioates and 6,6-dimethyl-4-(2-(propan-2-ylidene)hydrazinyl)-6,7-dihydro-2H-indazole-3(5H)-thione compounds have been investigated. Four of them, 13, 18, 19 and 20 inhibited PBMC proliferation induced by phytohemagglutinin (PHA) in a dose dependent manner with an IC50 of <= 20 mu M. The Th-1 cytokine, interleukin-2 (IL-2) in PHA/PMA-stimulated peripheral blood mononuclear cells (PBMCs) is significantly inhibited by 13, 19 and 20 with an IC50 of 8.4 +/- 0.4, 5.34 +/- 0.15 and 4.9 +/- 0.7 mu M, respectively. They also inhibited the PMA/lipopolysaccharide-induced proinflammatory cytokines, IL-1 beta and TNF-alpha production in human monocytic leukemia cells (THP-1), by 86%, 46% and 59.2% for IL-1 beta and by 83.8%, 48.2% and 58.7% for TNF-alpha, respectively. Only 20 showed significant suppressive activity against the phagocyte oxidative burst in a dose dependent manner, with an IC50 of 23.8 mu M. LPS-induced nitrites in mouse macrophages were found to be inhibited by compounds 6, 8, 13-15 and 19 with an IC50, which range between 7.7 and 63 mu M. The cytotoxicity for the active compounds was also studied on Rat Wistar Hepatocyte cell line, CC1 and the Mouse Fibroblast cell line 3T3 NIH in the presence of compounds using a standard MTT assay. Furthermore, structural-activity relationship using automated docking software revealed that active compounds 7, 13 and 19, adapted the same binding mode, however the most active compound 20 is found deeply inserted within the ligand binding site of IL-2, as multiple hydrophobic and hydrophilic key interactions stabilize the compound inside the binding site, thus contributing higher activity.[GRAPHICS]. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.003

文献信息

• Synthesis, biological evaluation, and molecular docking studies of benzyl, alkyl and glycosyl [2-(arylamino)-4,4-dimethyl-6-oxo-cyclohex-1-ene]carbodithioates, as potential immunomodulatory and immunosuppressive agents
  作者：El Sayed H. El Ashry、Mohammad R. Amer、Omer M. Abdalla、Aly A. Aly、Samreen Soomro、Almas Jabeen、Sobia Ahsan Halim、M. Ahmed Mesaik、Zaheer Ul-Haq

  DOI：10.1016/j.bmc.2012.03.003

  日期：2012.5

  The immunomodulating properties of functionalized [2-(arylamino)-4,4-dimethyl-6-oxo-cyclohex-1-ene] carbodithioates and 6,6-dimethyl-4-(2-(propan-2-ylidene)hydrazinyl)-6,7-dihydro-2H-indazole-3(5H)-thione compounds have been investigated. Four of them, 13, 18, 19 and 20 inhibited PBMC proliferation induced by phytohemagglutinin (PHA) in a dose dependent manner with an IC50 of <= 20 mu M. The Th-1 cytokine, interleukin-2 (IL-2) in PHA/PMA-stimulated peripheral blood mononuclear cells (PBMCs) is significantly inhibited by 13, 19 and 20 with an IC50 of 8.4 +/- 0.4, 5.34 +/- 0.15 and 4.9 +/- 0.7 mu M, respectively. They also inhibited the PMA/lipopolysaccharide-induced proinflammatory cytokines, IL-1 beta and TNF-alpha production in human monocytic leukemia cells (THP-1), by 86%, 46% and 59.2% for IL-1 beta and by 83.8%, 48.2% and 58.7% for TNF-alpha, respectively. Only 20 showed significant suppressive activity against the phagocyte oxidative burst in a dose dependent manner, with an IC50 of 23.8 mu M. LPS-induced nitrites in mouse macrophages were found to be inhibited by compounds 6, 8, 13-15 and 19 with an IC50, which range between 7.7 and 63 mu M. The cytotoxicity for the active compounds was also studied on Rat Wistar Hepatocyte cell line, CC1 and the Mouse Fibroblast cell line 3T3 NIH in the presence of compounds using a standard MTT assay. Furthermore, structural-activity relationship using automated docking software revealed that active compounds 7, 13 and 19, adapted the same binding mode, however the most active compound 20 is found deeply inserted within the ligand binding site of IL-2, as multiple hydrophobic and hydrophilic key interactions stabilize the compound inside the binding site, thus contributing higher activity.[GRAPHICS]. (C) 2012 Elsevier Ltd. All rights reserved.