6-amino-1,11-dichloro-6,7,12,13-tetrahydro-5,7-dioxoindolo[2,3-a]pyrrolo[3,4-c]carbazole | 183747-16-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-amino-1,11-dichloro-6,7,12,13-tetrahydro-5,7-dioxoindolo[2,3-a]pyrrolo[3,4-c]carbazole
• 英文别名: 5H-Indolo(2,3-a)pyrrolo(3,4-c)carbazole-5,7(6H)-dione, 6-amino-1,11-dichloro-12,13-dihydro-；13-amino-5,21-dichloro-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione
• CAS: 183747-16-2
• 化学式: C₂₀H₁₀Cl₂N₄O₂
• 分子量: 409.231
• InChiKey: ZYIYLFKDJSEYBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  95
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N,N-二甲基甲酰胺 、 6-amino-1,11-dichloro-6,7,12,13-tetrahydro-5,7-dioxoindolo[2,3-a]pyrrolo[3,4-c]carbazole 在 盐酸 作用下， 以93%的产率得到6-formamido-1,11-dichloro-6,7,12,13-tetrahydro-5,7-dioxoindolo[2,3-a]pyrrolo[3,4-c]carbazole
  参考文献：
  名称：

  Structure−Activity Relationships in a Series of Substituted Indolocarbazoles:  Topoisomerase I and Protein Kinase C Inhibition and Antitumoral and Antimicrobial Properties

  摘要：

  A series of compounds structurally related to staurosporine, rebeccamycin, and corresponding aglycones was synthesized, and their activities toward protein kinase C and topoisomerases I and II were tested together with their in vitro antitumor efficiency against murine B16 melanoma and P388 leukemia cells. Their antimicrobial activities were also examined against a Gram-negative bacterium (Escherichia coli), a yeast (Candida albicans), and three Gram-positive bacteria (Bacillus cereus, Streptomyces chartreusis, and Streptomyces griseus). To avoid side effects expected with protein kinase C inhibitors, we introduced substitution on the maleimide nitrogen and/or a sugar moiety linked to one of the indole nitrogens to obtain specific inhibitors of topoisomerase I with minimal activities on protein kinase C. As expected, these structures were inefficient on topoisomerase II, and some of them exhibited a strong activity against topoisomerase I. Generally, dechlorinated compounds were found to be more active than chlorinated analogues against both purified topoisomerase I and protein kinase C. On the other hand, opposite results were obtained in the cell antiproliferative assays. These results suggest lack of cell membrane permeability in the absence of the chlorine residue or cleavage of carbon-chlorine bonds inside the cell.

  DOI：

  10.1021/jm9603779
• 作为产物：
  描述：

  rebeccamycin 在 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以90%的产率得到6-amino-1,11-dichloro-6,7,12,13-tetrahydro-5,7-dioxoindolo[2,3-a]pyrrolo[3,4-c]carbazole
  参考文献：
  名称：

  Structure−Activity Relationships in a Series of Substituted Indolocarbazoles:  Topoisomerase I and Protein Kinase C Inhibition and Antitumoral and Antimicrobial Properties

  摘要：

  A series of compounds structurally related to staurosporine, rebeccamycin, and corresponding aglycones was synthesized, and their activities toward protein kinase C and topoisomerases I and II were tested together with their in vitro antitumor efficiency against murine B16 melanoma and P388 leukemia cells. Their antimicrobial activities were also examined against a Gram-negative bacterium (Escherichia coli), a yeast (Candida albicans), and three Gram-positive bacteria (Bacillus cereus, Streptomyces chartreusis, and Streptomyces griseus). To avoid side effects expected with protein kinase C inhibitors, we introduced substitution on the maleimide nitrogen and/or a sugar moiety linked to one of the indole nitrogens to obtain specific inhibitors of topoisomerase I with minimal activities on protein kinase C. As expected, these structures were inefficient on topoisomerase II, and some of them exhibited a strong activity against topoisomerase I. Generally, dechlorinated compounds were found to be more active than chlorinated analogues against both purified topoisomerase I and protein kinase C. On the other hand, opposite results were obtained in the cell antiproliferative assays. These results suggest lack of cell membrane permeability in the absence of the chlorine residue or cleavage of carbon-chlorine bonds inside the cell.

  DOI：

  10.1021/jm9603779

文献信息

• Structure−Activity Relationships in a Series of Substituted Indolocarbazoles:  Topoisomerase I and Protein Kinase C Inhibition and Antitumoral and Antimicrobial Properties
  作者：Elisabète Rodrigues Pereira、Laure Belin、Martine Sancelme、Michelle Prudhomme、Monique Ollier、Maryse Rapp、Danièle Sevère、Jean-François Riou、Doriano Fabbro、Thomas Meyer

  DOI：10.1021/jm9603779

  日期：1996.1.1

  A series of compounds structurally related to staurosporine, rebeccamycin, and corresponding aglycones was synthesized, and their activities toward protein kinase C and topoisomerases I and II were tested together with their in vitro antitumor efficiency against murine B16 melanoma and P388 leukemia cells. Their antimicrobial activities were also examined against a Gram-negative bacterium (Escherichia coli), a yeast (Candida albicans), and three Gram-positive bacteria (Bacillus cereus, Streptomyces chartreusis, and Streptomyces griseus). To avoid side effects expected with protein kinase C inhibitors, we introduced substitution on the maleimide nitrogen and/or a sugar moiety linked to one of the indole nitrogens to obtain specific inhibitors of topoisomerase I with minimal activities on protein kinase C. As expected, these structures were inefficient on topoisomerase II, and some of them exhibited a strong activity against topoisomerase I. Generally, dechlorinated compounds were found to be more active than chlorinated analogues against both purified topoisomerase I and protein kinase C. On the other hand, opposite results were obtained in the cell antiproliferative assays. These results suggest lack of cell membrane permeability in the absence of the chlorine residue or cleavage of carbon-chlorine bonds inside the cell.