N-(9-(2-(benzyloxy)phenyl)-1,2,3,4,5,6,7,8-octahydro-3,3,6,6-tetramethyl-1,8-dioxoacridin-10(9H)-yl)-4-nitrobenzamide | 1374607-33-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(9-(2-(benzyloxy)phenyl)-1,2,3,4,5,6,7,8-octahydro-3,3,6,6-tetramethyl-1,8-dioxoacridin-10(9H)-yl)-4-nitrobenzamide
• 英文别名: 4-nitro-N-[3,3,6,6-tetramethyl-1,8-dioxo-9-(2-phenylmethoxyphenyl)-4,5,7,9-tetrahydro-2H-acridin-10-yl]benzamide
• CAS: 1374607-33-6
• 化学式: C₃₇H₃₇N₃O₆
• 分子量: 619.717
• InChiKey: VAWTXARDQRXEAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  46
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5,5-二甲基-1,3-环己二酮 、 4-硝基苯酰肼 、 2-苄氧基苯甲醛 在 盐酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以77.2%的产率得到N-(9-(2-(benzyloxy)phenyl)-1,2,3,4,5,6,7,8-octahydro-3,3,6,6-tetramethyl-1,8-dioxoacridin-10(9H)-yl)-4-nitrobenzamide
  参考文献：
  名称：

  Novel acridinedione derivatives: Design, synthesis, SIRT1 enzyme and tumor cell growth inhibition studies

  摘要：

  A new scaffold N-(9-(ortho/meta/para-(benzyloxy)phenyl)-3,3,6,6-tetramethyl-1,8-dioxo-1,2,3,4,5,6,7,8-octahydroacridin- 10(9H)-yl) isonicotinamide (H1-3) was discovered as a hSIRT1 inhibitor through virtual screening of in-house database. Based on these hits, a library of compounds were designed, synthesized and tested for in vitro hSIRT1 activity. The most potent compound 4d in the series showed a significant inhibition of SIRT1 activity. Further antitumor studies of compound 4d, showed a dose dependent increase in acetylation of p53K382 and decrease in SIRT1 with an IC50 of 0.25 mu M in MDA-MB231 breast cancer cell lines. Individual 3D-QSAR analysis using Schrodinger showed distribution of hydrophobic and non polar positive co-efficient at ortho position essential for bioactivity based on 4d. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.030

文献信息

• Novel acridinedione derivatives: Design, synthesis, SIRT1 enzyme and tumor cell growth inhibition studies
  作者：Mallika Alvala、Shubhmita Bhatnagar、Alvala Ravi、Variam Ullas Jeankumar、Thimmappa H Manjashetty、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.bmcl.2012.03.030

  日期：2012.5

  A new scaffold N-(9-(ortho/meta/para-(benzyloxy)phenyl)-3,3,6,6-tetramethyl-1,8-dioxo-1,2,3,4,5,6,7,8-octahydroacridin- 10(9H)-yl) isonicotinamide (H1-3) was discovered as a hSIRT1 inhibitor through virtual screening of in-house database. Based on these hits, a library of compounds were designed, synthesized and tested for in vitro hSIRT1 activity. The most potent compound 4d in the series showed a significant inhibition of SIRT1 activity. Further antitumor studies of compound 4d, showed a dose dependent increase in acetylation of p53K382 and decrease in SIRT1 with an IC50 of 0.25 mu M in MDA-MB231 breast cancer cell lines. Individual 3D-QSAR analysis using Schrodinger showed distribution of hydrophobic and non polar positive co-efficient at ortho position essential for bioactivity based on 4d. (C) 2012 Elsevier Ltd. All rights reserved.