12-(6-chloro-6-deoxy-4-O-methyl-β-D-glucopyranosyl)-6,7,12,13-tetrahydro(5H)-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7-dione | 643064-13-5

• 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: 12-(6-chloro-6-deoxy-4-O-methyl-β-D-glucopyranosyl)-6,7,12,13-tetrahydro(5H)-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7-dione
• 英文别名: 12-(6-chloro-6-deoxy-4-O-methyl-β-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione；12-(6-chloro-6-deoxy-4-O-methyl-beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione；3-[(2R,3R,4R,5S,6S)-6-(chloromethyl)-3,4-dihydroxy-5-methoxyoxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaene-12,14-dione
• CAS: 643064-13-5
• 化学式: C₂₇H₂₂ClN₃O₆
• 分子量: 519.941
• InChiKey: QLUHSOUKVKOAMO-HHJYCPGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  12-(6-chloro-6-deoxy-4-O-methyl-β-D-glucopyranosyl)-6,7,12,13-tetrahydro(5H)-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7-dione 在 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 168000.0h， 以89%的产率得到12-(6-deoxy-6-iodo-4-O-methyl-β-D-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：

  Rebeccamycin analogues bearing amine substituents or other groups on the sugar moiety

  摘要：

  In the course of structure-activity relationship studies on rebeccamycin analogues, a series of compounds bearing an amino function on the sugar moiety were synthesized with the aim of improving the solubility and interaction with the macromolecular target(s). The syntheses of amino derivatives and the corresponding chloro, iodo and azido intermediates are described. Their interaction with DNA and effects on human DNA topoisomerases I and II were investigated. Their antimicrobial activities against two Gram-positive bacteria, Bacillus cereus and Streptomyces chartreusis, a Gram-negative bacterium Escherichia coli and a yeast Candida albicans were also determined. 6'-Amino compound 7 and 6'-N-methylamino 14 very efficiently inhibit the growth of E. coli. The introduction of an amino group at the 6'-position strongly enhances the capacity of the drugs to interact with DNA but almost abolishes their poisoning effect on topoisomerase I. Unlike the vast majority of rebeccamycin analogues previously studied, the newly designed compounds do not stimulate DNA cleavage by topoisomerase I. The enhanced capacity of the 6'-amino glycosyl rebeccamycin derivatives to bind to DNA likely account for the improved biological profiles. DNA and topoisomerase I represent two independent targets which can both be used for the development of antitumor rebeccamycin derivatives. (C) 2003 Elsevier Ltd All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00343-2
• 作为产物：
  描述：

  5H-indolo(2,3-a)pyrrolo(3,4-c)carbazole-5,7(6h)-dione,1,11-dichloro-12,13-dihydro-12-(4-omethyl-beta-d-glucopyranosyl) 在 吡啶 、 四氯化碳 、 三苯基膦 作用下， 反应 3.0h， 生成 12-(6-chloro-6-deoxy-4-O-methyl-β-D-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：

  Novel hydroxyalkyl indolocarbazole derivatives, preparation method and pharmaceutical compositions containing the same

  摘要：

  化合物的结构式（I）如下：其中：R1和R2分别代表从氢、烷基、芳基烷基、羟基、羟基烷基、二羟基烷基、烷氧基、烷氧基烷基、氨基和氨基烷基（可选择取代）中选择的基团，Ra和Rb各自代表一个烷基链，X1、X2和X3分别代表从羟基、烷氧基、芳氧基、芳基烷氧基、烷基、氨基（可选择取代）、卤素、烷基羰氧基和叠氮基中选择的基团，X4代表一个甲基亚甲基基团或一个按照说明中定义的公式—Rc—X1的基团，它们的异构体以及它们与药学上可接受的酸或碱形成的加合盐。

  公开号：

  US20040242508A1

文献信息

• Novel hydroxyalkyl indolocarbazole derivatives, preparation method and pharmaceutical compositions containing the same
  申请人：——

  公开号：US20040242508A1

  公开（公告）日：2004-12-02

  Compound of formula (I): 1 wherein: R 1 and R 2 each represents a group selected from hydrogen, alkyl, arylalkyl, hydroxy, hydroxyalkyl, dihydroxyalkyl, alkoxy, alkoxyalkyl, amino and aminoalkyl (optionally substituted), Ra and Rb each represents an alkylene chain, X 1 , X 2 and X 3 each represents a group selected from hydroxy, alkoxy, aryloxy, arylalkoxy, alkyl, amino (optionally substituted), halogen, alkylcarbonyloxy and azido, X 4 represents a methylidene group or a group of formula —Rc—X 1 as defined in the description, their isomers and also their addition salts with a pharmaceutically acceptable acid or base.

  化合物的结构式（I）如下：其中：R1和R2分别代表从氢、烷基、芳基烷基、羟基、羟基烷基、二羟基烷基、烷氧基、烷氧基烷基、氨基和氨基烷基（可选择取代）中选择的基团，Ra和Rb各自代表一个烷基链，X1、X2和X3分别代表从羟基、烷氧基、芳氧基、芳基烷氧基、烷基、氨基（可选择取代）、卤素、烷基羰氧基和叠氮基中选择的基团，X4代表一个甲基亚甲基基团或一个按照说明中定义的公式—Rc—X1的基团，它们的异构体以及它们与药学上可接受的酸或碱形成的加合盐。
• Rebeccamycin analogues bearing amine substituents or other groups on the sugar moiety
  作者：Fabrice Anizon、Pascale Moreau、Martine Sancelme、William Laine、Christian Bailly、Michelle Prudhomme

  DOI：10.1016/s0968-0896(03)00343-2

  日期：2003.8

  In the course of structure-activity relationship studies on rebeccamycin analogues, a series of compounds bearing an amino function on the sugar moiety were synthesized with the aim of improving the solubility and interaction with the macromolecular target(s). The syntheses of amino derivatives and the corresponding chloro, iodo and azido intermediates are described. Their interaction with DNA and effects on human DNA topoisomerases I and II were investigated. Their antimicrobial activities against two Gram-positive bacteria, Bacillus cereus and Streptomyces chartreusis, a Gram-negative bacterium Escherichia coli and a yeast Candida albicans were also determined. 6'-Amino compound 7 and 6'-N-methylamino 14 very efficiently inhibit the growth of E. coli. The introduction of an amino group at the 6'-position strongly enhances the capacity of the drugs to interact with DNA but almost abolishes their poisoning effect on topoisomerase I. Unlike the vast majority of rebeccamycin analogues previously studied, the newly designed compounds do not stimulate DNA cleavage by topoisomerase I. The enhanced capacity of the 6'-amino glycosyl rebeccamycin derivatives to bind to DNA likely account for the improved biological profiles. DNA and topoisomerase I represent two independent targets which can both be used for the development of antitumor rebeccamycin derivatives. (C) 2003 Elsevier Ltd All rights reserved.