6-dodecanoylamido-4-methyl-8-(β-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-dodecanoylamido-4-methyl-8-(β-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine
• 英文别名: N-[2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-methyl-2,6,7,9,11-pentazatricyclo[6.3.1.04,12]dodeca-1(12),3,5,8,10-pentaen-5-yl]dodecanamide
• 化学式: C₂₅H₃₈N₆O₅
• 分子量: 502.614
• InChiKey: VQURNYFYJQZCST-OALHLCOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  曲西瑞宾 在 吡啶 、 氨 作用下， 以 甲醇 为溶剂， 反应 40.0h， 生成 6-dodecanoylamido-4-methyl-8-(β-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine
  参考文献：
  名称：

  6-N-Acyltriciribine Analogues:  Structure−Activity Relationship between Acyl Carbon Chain Length and Activity against HIV-1

  摘要：

  Triciribine (TCN) and triciribine-5'-monophosphate (TCN-P) are active against HIV-1 at submicromolar concentrations. In an effort to improve and better understand this activity, we have conducted a structure-activity relationship study to explore the tolerance of TCN to structural modifications at the 6-position. A number of 6-N-acyltriciribine analogues were synthesized and evaluated for antiviral activity and cytotoxicity. The cytotoxicity of these compounds was minimal in three human cell lines (KB, CEM-SS cells, and human foreskin fibroblasts (HFF)). The compounds were marginally active or inactive against herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). In contrast, most of the compounds exhibited moderate to high activity against human immunodeficiency virus type 1 (HIV-1), IC50's = 0.03 to 1 mu M. This structure-activity relationship study identified the N-heptanoyl group as having the optimal carbon chain length. This compound was as active against HIV-1 as TCN and TCN-P. Reverse phase HPLC of extracts from uninfected cells treated with 6-N-acyltriciribines detected sufficient TCN-P to account for anti-HIV activity thereby suggesting a prodrug effect. Studies in an adenosine kinase deficient cell line showed that the 6-N-acyl derivative was not phosphorylated directly but first was metabolized to triciribine which then was converted to TCN-P.

  DOI：

  10.1021/jm990236h

文献信息

• 6-<i>N</i>-Acyltriciribine Analogues:  Structure−Activity Relationship between Acyl Carbon Chain Length and Activity against HIV-1
  作者：Anthony R. Porcari、Roger G. Ptak、Katherine Z. Borysko、Julie M. Breitenbach、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm990236h

  日期：2000.6.1

  Triciribine (TCN) and triciribine-5'-monophosphate (TCN-P) are active against HIV-1 at submicromolar concentrations. In an effort to improve and better understand this activity, we have conducted a structure-activity relationship study to explore the tolerance of TCN to structural modifications at the 6-position. A number of 6-N-acyltriciribine analogues were synthesized and evaluated for antiviral activity and cytotoxicity. The cytotoxicity of these compounds was minimal in three human cell lines (KB, CEM-SS cells, and human foreskin fibroblasts (HFF)). The compounds were marginally active or inactive against herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). In contrast, most of the compounds exhibited moderate to high activity against human immunodeficiency virus type 1 (HIV-1), IC50's = 0.03 to 1 mu M. This structure-activity relationship study identified the N-heptanoyl group as having the optimal carbon chain length. This compound was as active against HIV-1 as TCN and TCN-P. Reverse phase HPLC of extracts from uninfected cells treated with 6-N-acyltriciribines detected sufficient TCN-P to account for anti-HIV activity thereby suggesting a prodrug effect. Studies in an adenosine kinase deficient cell line showed that the 6-N-acyl derivative was not phosphorylated directly but first was metabolized to triciribine which then was converted to TCN-P.