(6-chloro-1H-indol-3-yl)oxoacetic acid methylester

• 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-chloro-1H-indol-3-yl)oxoacetic acid methylester
• 英文别名: methyl 7-chloro-α-oxo-1H-indole-3-acetate；Methyl 2-(7-Chloro-3-indolyl)-2-oxoacetate；methyl 2-(7-chloro-1H-indol-3-yl)-2-oxoacetate
• 化学式: C₁₁H₈ClNO₃
• 分子量: 237.642
• InChiKey: WAJWUEJTSIZVDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-甲基-1-哌嗪)-4-喹唑啉乙酰胺 、 (6-chloro-1H-indol-3-yl)oxoacetic acid methylester 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 生成 3-(7-chloro-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)-quinazolin-4-yl]pyrrole-2,5-dione
  参考文献：
  名称：

  Structure–Activity Relationship and Pharmacokinetic Studies of Sotrastaurin (AEB071), a Promising Novel Medicine for Prevention of Graft Rejection and Treatment of Psoriasis

  摘要：

  Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure - activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to contribute to its in vivo efficacy.

  DOI：

  10.1021/jm200469u
• 作为产物：
  描述：

  7-氯吲哚 、 草酰氯 、 sodium methylate 生成 (6-chloro-1H-indol-3-yl)oxoacetic acid methylester
  参考文献：
  名称：

  Synthesis of Rebeccamycin and 11-Dechlororebeccamycin

  摘要：

  Glycosylated 7-chloroindole-3-acetamide 9, prepared in four steps and 26% yield from 7-chloroindole (1), was condensed with methyl 7-chloroindole-3-glyoxylate 11 and methyl indole-3-glyoxylate 12 to provide bisindolylmaleimides 7 and 8 in 86% and 84% yield, respectively. Oxidation of 7 and 8 followed by debenzylation provided a new approach to the synthesis of rebeccamycin and completed for the first time a synthesis of 11-dechlororebeccamycin.

  DOI：

  10.1021/jo982277b

文献信息

• Synthesis of Rebeccamycin and 11-Dechlororebeccamycin
  作者：Margaret M. Faul、Leonard L. Winneroski、Christine A. Krumrich

  DOI：10.1021/jo982277b

  日期：1999.4.1

  Glycosylated 7-chloroindole-3-acetamide 9, prepared in four steps and 26% yield from 7-chloroindole (1), was condensed with methyl 7-chloroindole-3-glyoxylate 11 and methyl indole-3-glyoxylate 12 to provide bisindolylmaleimides 7 and 8 in 86% and 84% yield, respectively. Oxidation of 7 and 8 followed by debenzylation provided a new approach to the synthesis of rebeccamycin and completed for the first time a synthesis of 11-dechlororebeccamycin.
• Structure–Activity Relationship and Pharmacokinetic Studies of Sotrastaurin (AEB071), a Promising Novel Medicine for Prevention of Graft Rejection and Treatment of Psoriasis
  作者：Jürgen Wagner、Peter von Matt、Bernard Faller、Nigel G. Cooke、Rainer Albert、Richard Sedrani、Hansjörg Wiegand、Christian Jean、Christian Beerli、Gisbert Weckbecker、Jean-Pierre Evenou、Gerhard Zenke、Sylvain Cottens

  DOI：10.1021/jm200469u

  日期：2011.9.8

  Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure - activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to contribute to its in vivo efficacy.