1,11-dichloro-12[4-O-methyl-β-D-(2'-O-tosyl)glucopyranosyl]-6,7,12,13-tetrahydro(5H)-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7-dione | 215796-54-6

• 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: 1,11-dichloro-12[4-O-methyl-β-D-(2'-O-tosyl)glucopyranosyl]-6,7,12,13-tetrahydro(5H)-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7-dione
• 英文别名: 1,11-Dichloro-12-[4-o-methyl-2-o-tosyl-beta-d-glucopyranosyl]-6,7,12,13-tetrahydro-(5h)-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione；[(2R,3R,4S,5S,6R)-2-(5,21-dichloro-12,14-dioxo-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-nonaen-3-yl)-4-hydroxy-6-(hydroxymethyl)-5-methoxyoxan-3-yl] 4-methylbenzenesulfonate
• CAS: 215796-54-6
• 化学式: C₃₄H₂₇Cl₂N₃O₉S
• 分子量: 724.575
• InChiKey: OEWRXTSXFYOXPZ-ROAFZNMGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  49
• 可旋转键数：
  6
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1,11-dichloro-12[4-O-methyl-β-D-(2'-O-tosyl)glucopyranosyl]-6,7,12,13-tetrahydro(5H)-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7-dione 在 palladium on activated charcoal 盐酸 、 sodium azide 、 ammonium formate 、 汞 、 锌 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 196.0h， 生成 12,13-[1,2-(4-O-methyl-D-mannopyranosyl)]-6,7,12,13-tetrahydro-5-oxo-(5H)-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7-dione
  参考文献：
  名称：

  Syntheses, biochemical and biological evaluation of staurosporine analogues from the microbial metabolite rebeccamycin

  摘要：

  The indolocarbazole antibiotics staurosporine and rebeccamycin (1) are potent antitumor drugs targeting protein kinase C and topoisomerase I, respectively. To obtain staurosporine analogues from rebeccamycin, different structural modifications were performed: coupling of the sugar moiety to the second indole nitrogen, dechlorination and then reduction of the imide function to amide. The newly synthesized compounds (3-6) were tested for their abilities to bind to DNA and to inhibit topoisomerase I and protein kinase C, Their antiproliferative effects in vitro against B16 melanoma and P388 leukemia (including the related P388CPT cell line resistant to camptothecin) as well as their anti-HIV-l and antimicrobial activities against various strains of microorganisms were determined. The cytotoxicity of the dechlorinated imide analogue 5 correlates well with its DNA binding and anti-topoisomerase I activities. These findings provide guidance for the development of new topoisomerase I-targeted antitumor indolocarbazoles equipped with a carbohydrate attached to the two indole nitrogens. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00096-0
• 作为产物：
  描述：

  蝴蝶霉素 、 对甲苯磺酰氯 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以47%的产率得到1,11-dichloro-12[4-O-methyl-β-D-(2'-O-tosyl)glucopyranosyl]-6,7,12,13-tetrahydro(5H)-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7-dione
  参考文献：
  名称：

  Syntheses, biochemical and biological evaluation of staurosporine analogues from the microbial metabolite rebeccamycin

  摘要：

  The indolocarbazole antibiotics staurosporine and rebeccamycin (1) are potent antitumor drugs targeting protein kinase C and topoisomerase I, respectively. To obtain staurosporine analogues from rebeccamycin, different structural modifications were performed: coupling of the sugar moiety to the second indole nitrogen, dechlorination and then reduction of the imide function to amide. The newly synthesized compounds (3-6) were tested for their abilities to bind to DNA and to inhibit topoisomerase I and protein kinase C, Their antiproliferative effects in vitro against B16 melanoma and P388 leukemia (including the related P388CPT cell line resistant to camptothecin) as well as their anti-HIV-l and antimicrobial activities against various strains of microorganisms were determined. The cytotoxicity of the dechlorinated imide analogue 5 correlates well with its DNA binding and anti-topoisomerase I activities. These findings provide guidance for the development of new topoisomerase I-targeted antitumor indolocarbazoles equipped with a carbohydrate attached to the two indole nitrogens. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00096-0

文献信息

• New compounds of 12,13-(pyranosyl)-indolo[2,3-a]pyrrolo[3,4-c]carbazole and 12,13-(pyranosyl)-furo[3,4-c]indolo[2,3-a]carbazole
  申请人：——

  公开号：US20020055510A1

  公开（公告）日：2002-05-09

  A compound selected from those of formula (I): 1 wherein: R 1 and R 2 , which may be identical or different, represent a group of formula U-V wherein U represents single bond, or alkylene which is optionally substituted and/or unsaturated, and V is as defined in the description, G represents oxygen, or NR 3 wherein R 3 is as defined in the description, X represents hydrogen, hydroxy, alkoxy, mercapto or alkylthio, Y represents hydrogen, or X+Y represents carbonyl, X 1 represents hydrogen, hydroxy, alkoxy, mercapto or alkylthio, Y 1 represents hydrogen, or X 1 +Y 1 represents carbonyl, R 4 , R 5 , and R 6 are as defined in the description, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof, and medicinal products containing the same are useful in the treatment of cancer.

  从公式（I）中选择的化合物：其中：R1和R2，可以相同也可以不同，表示公式U-V的基团，其中U表示单键，或者是可以选择性取代和/或不饱和的烷基，而V如描述中所定义，G表示氧，或者是NR3，其中R3如描述中所定义，X表示氢，羟基，烷氧基，巯基或烷硫基，Y表示氢，或者X+Y表示羰基，X1表示氢，羟基，烷氧基，巯基或烷硫基，Y1表示氢，或者X1+Y1表示羰基，R4、R5和R6如描述中所定义，其异构体和药学上可接受的酸或碱盐，以及含有它们的药物制剂在癌症治疗中有用。
• 12,13-(pyranosyl)-indolo[2,3-a]pyrrolo[3,4-c]carbazole and 12,13-(pyranosyl)-furo[3,4-c]indolo[2,3-a]carbazoles
  申请人：Les Laboratoires Servier

  公开号：US06569858B2

  公开（公告）日：2003-05-27

  A compound selected from those of formula (I): wherein: R1 and R2, which may be identical or different, represent a group of formula U-V wherein U represents single bond, or alkylene which is optionally substituted and/or unsaturated, and V is as defined in the description, G represents oxygen, or NR3 wherein R3 is as defined in the description, X represents hydrogen, hydroxy, alkoxy, mercapto or alkylthio, Y represents hydrogen, or X+Y represents carbonyl, X1 represents hydrogen, hydroxy, alkoxy, mercapto or alkylthio, Y1 represents hydrogen, or X1+Y1 represents carbonyl, R4, R5, and R6 are as defined in the description, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof, and medicinal products containing the same are useful in the treatment of cancer.

  从式(I)中选择的化合物，其中：R1和R2可以相同或不同，表示式U-V的基团，其中U表示单键，或者是选择性取代和/或不饱和的烷基，V如描述所定义，G表示氧或NR3，其中R3如描述所定义，X表示氢、羟基、烷氧基、巯基或烷基硫，Y表示氢，或X+Y表示羰基，X1表示氢、羟基、烷氧基、巯基或烷基硫，Y1表示氢，或X1+Y1表示羰基，R4、R5和R6如描述所定义，其异构体和药学上可接受的酸或碱盐，以及含有它们的药物制剂在癌症治疗中有用。
• Semi-synthesis, topoisomerase I and kinases inhibitory properties, and antiproliferative activities of new rebeccamycin derivatives
  作者：Pascale Moreau、Nathalie Gaillard、Christelle Marminon、Fabrice Anizon、Nathalie Dias、Brigitte Baldeyrou、Christian Bailly、Alain Pierré、John Hickman、Bruno Pfeiffer、Pierre Renard、Michelle Prudhomme

  DOI：10.1016/j.bmc.2003.09.014

  日期：2003.11

  In the course of structure-activity relationship studies, new rebeccamycin derivatives substituted in 3,9-positions on the indolocarbazole framework, and a 2,3-anhydro derivative were prepared by semi-synthesis from rebeccamycin. The antiproliferative activities against nine tumor cell lines were determined and the effect on the cell cycle of murine leukemia L1210 cells was examined. Their DNA binding properties and inhibitory properties toward topoisomerase I and three kinases PKCzeta, CDKI/cyclin B, CDK5/p25 and a phosphatase cdc25A were evaluated. The 3,9-dihydroxy derivative is the most efficient compound of this series toward CDKI/cyclin B and CDK5/p25. It is also characterized as a DNA binding topoisomerase I poison. Its broad spectrum of molecular activities likely accounts for its cytotoxic potential. This compound which displays a tumor cell line-selectivity may represent a new lead for subsequent drug design in this series of glycosylated indolocarbazoles. (C) 2003 Elsevier Ltd. All rights reserved.
• US6569858B2
  申请人：——

  公开号：US6569858B2

  公开（公告）日：2003-05-27
• Syntheses, biochemical and biological evaluation of staurosporine analogues from the microbial metabolite rebeccamycin
  作者：Fabrice Anizon、Pascale Moreau、Martine Sancelme、Aline Voldoire、Michelle Prudhomme、Monique Ollier、Danièle Sevère、Jean-François Riou、Christian Bailly、Doriano Fabbro、Thomas Meyer、A.M Aubertin

  DOI：10.1016/s0968-0896(98)00096-0

  日期：1998.9

  The indolocarbazole antibiotics staurosporine and rebeccamycin (1) are potent antitumor drugs targeting protein kinase C and topoisomerase I, respectively. To obtain staurosporine analogues from rebeccamycin, different structural modifications were performed: coupling of the sugar moiety to the second indole nitrogen, dechlorination and then reduction of the imide function to amide. The newly synthesized compounds (3-6) were tested for their abilities to bind to DNA and to inhibit topoisomerase I and protein kinase C, Their antiproliferative effects in vitro against B16 melanoma and P388 leukemia (including the related P388CPT cell line resistant to camptothecin) as well as their anti-HIV-l and antimicrobial activities against various strains of microorganisms were determined. The cytotoxicity of the dechlorinated imide analogue 5 correlates well with its DNA binding and anti-topoisomerase I activities. These findings provide guidance for the development of new topoisomerase I-targeted antitumor indolocarbazoles equipped with a carbohydrate attached to the two indole nitrogens. (C) 1998 Elsevier Science Ltd. All rights reserved.